Rotavirus infections cause severe gastroenteritis and dehydration in young children and animals worldwide,leading to high rates of morbidity and mortality,predominantly in low-and middleincome countries.In the past de...Rotavirus infections cause severe gastroenteritis and dehydration in young children and animals worldwide,leading to high rates of morbidity and mortality,predominantly in low-and middleincome countries.In the past decade,substantial progress has been made in the development and implementation of rotavirus vaccines,which have been essential in alleviating the global burden of this disease,not only in human being but also in livestock species like calves and piglets,where these infections can cause significant economic losses.By synthesizing the latest research and real-world evidence,this review article is designated to provide deep insights into the current state of rotavirus vaccine technology and its global implementation as well as the application of rotavirus vaccines in veterinary settings and their importance in controlling zoonotic transmission and maintaining food security.展开更多
As an emerging genotype,the G9 genotype rotaviruses(RVs)are widespread among humans and pigs,and have been reported in many countries and regions in the recent years.Moreover,porcine G9 strains could cross the intersp...As an emerging genotype,the G9 genotype rotaviruses(RVs)are widespread among humans and pigs,and have been reported in many countries and regions in the recent years.Moreover,porcine G9 strains could cross the interspecies barrier to infect human.To investigate the epidemic trends of porcine G9 strains as well as the cross-immunoreactivity among different isolates,an epidemiological investigation about porcine G9 genotype RVs(PoRVs)was performed during the period 2020-2023 in multiple provinces of China.A total of nine representative strains were identified.The phylogenetic analysis based on viral VP7 gene showed that these strains mainly clustered with lineages Ⅲ and Ⅵ,which revealed the predominant G9 PoRVs in China.Moreover,a new lineage,lineage Ⅶ,was identified,and strains of this lineage were found to be circulating in Guangdong and Taiwan.Except lineages Ⅰ and Ⅳ,some isolates from other lineages could co-circulate in pigs and humans.Three G9 strains,namely 923H,923E,and 923X,which belonged to the largest sub-lineage Ⅲ,were isolated.Then,the significant cross-reactivity was observed among strains of the same or different lineages.This study is the first to systematically investigate the genetic and immunogenetic characteristics of porcine G9 genotype rotavirus in China,as well as the potential cross-species transmission between pigs and humans,providing a valuable direction for the effective prevention of porcine rotavirus.展开更多
The original version of Figure 2 contained the following inaccuracies:Rotarix was incorrectly shown as a 3-dose vaccine instead of a 2-dose vaccine;RotaTeq and Rotasiil were incorrectly shown as 2-dose vaccines instea...The original version of Figure 2 contained the following inaccuracies:Rotarix was incorrectly shown as a 3-dose vaccine instead of a 2-dose vaccine;RotaTeq and Rotasiil were incorrectly shown as 2-dose vaccines instead of 3-dose vaccines;Polyvac was incorrectly shown as a 3-dose vaccine instead of a 2-dose regimen;and the LLR vaccine should have been indicated as a single primary dose followed by annual boosters between 2 months and 3 years of age.展开更多
BACKGROUND Rotavirus(RV),a primary cause of diarrhea-related mortality in 2021,has been shown to damage intestinal epithelial cells while upregulating intestinal stem cells(ISCs)activities.ISCs within the crypt niche ...BACKGROUND Rotavirus(RV),a primary cause of diarrhea-related mortality in 2021,has been shown to damage intestinal epithelial cells while upregulating intestinal stem cells(ISCs)activities.ISCs within the crypt niche drive the continuous self-renewal of intestinal epithelium,preserving its barrier functions.Paneth cells secrete antimicrobial peptide and signaling molecules within the intestine crypt,thereby playing a crucial role in intestinal immune defense and providing ISCs functional support.However,the regulatory function of Paneth cells under pathological conditions,such as RV infection,remains unclear.AIM To determine the impact of RV infection on Paneth cells and how Paneth cells regulate ISCs during intestinal injury repair.METHODS We constructed a reference genome for the RV enteric cytopathogenic human orphan virus strain and reanalyzed published single-cell RNA sequencing data to investigate Paneth cell responses to RV-induced intestinal injury.We derived Paneth-ISC communication networks using CellChat,tracked ISC differentiation with pseudotime analysis,and validated our findings in leucine-rich repeat-containing G protein-coupled receptor 5-enhanced green fluorescent protein-internal ribosomal entry site-Cre recombinase estrogen receptor variant 2 mice and organoids via immunofluorescence,flow cytometry,and reverse transcription quantitative polymerase chain reaction.RESULTS We found that RV directly infects Paneth cells,leading to a reduction in mature Paneth cells and an increase in kallikrein 1-high immature Paneth cells.Paneth-ISC communication was significantly enhanced.In particular,the bone morphogenic protein 7(BMP7)-activin A receptor type 2B/BMP receptor type 1A-Smad pathway was upregulated post-infection,suggesting that Paneth cells suppress excessive ISC proliferation.Functional validation confirmed activation of this pathway.CONCLUSION Paneth cells regulate ISC proliferation during RV infection by activating BMP7 signaling,limiting excessive stem cell expansion and preserving crypt homeostasis for effective epithelial repair.展开更多
Objective The objective of our study was to evaluate the vaccine effectiveness(VE)of the pentavalent rotavirus vaccine(RV5)among<5-year-old children in three provinces of China during 2020-2024 via a propensity sco...Objective The objective of our study was to evaluate the vaccine effectiveness(VE)of the pentavalent rotavirus vaccine(RV5)among<5-year-old children in three provinces of China during 2020-2024 via a propensity score-matched test-negative case-control study.Methods Electronic health records and immunization information systems were used to obtain data on acute gastroenteritis(AGE)cases tested for rotavirus(RV)infection.RV-positive cases were propensity score matched with RV-negative controls for age,visit month,and province.Results The study included 27,472 children with AGE aged 8 weeks to 4 years at the time of AGE diagnosis;7.98%(2,192)were RV-positive.The VE(95%confidence interval,CI)of 1-2 and 3 doses of RV5 against any medically attended RV infection(inpatient or outpatient)was 57.6%(39.8%,70.2%)and 67.2%(60.3%,72.9%),respectively.Among children who received the 3rd dose before turning 5 months of age,3-dose VE decreased from 70.4%(53.9%,81.1%)(<5 months since the 3rd dose)to 63.0%(49.1%,73.0%)(≥1 year since the 3rd dose).The three-dose VE rate was 69.4%(41.3%,84.0%)for RVGE hospitalization and 57.5%(38.9%,70.5%)for outpatient-only medically attended RVGE.Conclusion Three-dose RV5 VE against rotavirus gastroenteritis(RVGE)in children aged<5 years was higher than 1-2-dose VE.Three-dose VE decreased with time since the 3rd dose in children who received the 3rd dose before turning five months of age,but remained above 60%for at least one year.VE was higher for RVGE hospitalizations than for medically attended outpatient visits.展开更多
Enteric viruses are the most common cause of acute gastroenteritis （AGE） in young children and a significant public health problem globally. Hospital admissions of children under 5 years of age with diarrhea are pri...Enteric viruses are the most common cause of acute gastroenteritis （AGE） in young children and a significant public health problem globally. Hospital admissions of children under 5 years of age with diarrhea are primarily associated with group A rotavirus （RVA） infection. In this retrospective study, the population structure of viruses linked to AGE etiology in young children hospitalized with AGE in Moscow was evaluated, and molecular characterization of RYA strains was performed. Fecal specimens were collected from children under 5 years old hospitalized with AGE between 2009 and 2014 in Moscow, Russia. Multiplex real-time reverse transcription PCR was used to detect enteric viruses and for G/[P]-genotyping of isolated RVAs. Sequencing of RVA VP7 and VP4 cDNA fragments was used to validate the data obtained by PCR- genotyping. The main causes for hospitalization of children with AGE were RVA （40.1%）, followed by noroviruses （11.4%）, while adenoviruses, astroviruses, sapoviruses, enteroviruses, and orthoreoviruses were detected in 4.7%, 1.9%, 1.4%, 1.2%, and 0.2% of samples tested, respectively. Nosocomial infections, predominantly associated with RVAs and noroviruses, were detected in 24.8% of cases and occurred significantly more frequently in younger infants. The predominant RVA genotype was G4P[8], detected in 38.7% of RVA-positive cases, whereas genotypes G1P[8], G9P[8], G3P[8], and G2P[4] were found in 11.8%, 6.6%, 4.2%, and 3.3% of cases, respectively. Together, the presence of circulating RVA strains with rare VP7 and VP4 gene variants （G6 and P[9]） highlights the need to conduct continuous epidemiological monitoring of RVA infection.展开更多
The oral hexavalent live human-bovine reassortant rotavirus vaccine(RV6)developed by Wuhan Institute of Biological Products Co.,Ltd(WIBP)has finished a randomized,placebo-controlled phase III clinical trial in four pr...The oral hexavalent live human-bovine reassortant rotavirus vaccine(RV6)developed by Wuhan Institute of Biological Products Co.,Ltd(WIBP)has finished a randomized,placebo-controlled phase III clinical trial in four provinces of China in 2021.The trail demonstrated that RV6 has a high vaccine efficacy against the prevalent strains and is safe for use in infants.During the phase III clinical trial(2019–2021),200 rotavirus-positive fecal samples from children with RV gastroenteritis(RVGE)were further studied.Using reverse transcription-polymerase chain reaction and high-throughput sequencing,VP7 and VP4 sequences were obtained and their genetic characteristics,as well as the differences in antigenic epitopes of VP7,were analyzed in detail.Seven rotavirus genotypes were identified.The predominant rotavirus genotype was G9P[8](77.0%),followed by prevalent strains G8P[8](8.0%),G3P[8](3.5%),G3P[9](1.5%),G1P[8](1.0%),G2P[4](1.0%),and G4P[6](1.0%).The amino acid sequence identities of G1,G2,G3,G4,G8,and G9 genotypes of isolates compared to the vaccine strains were 98.8%,98.2%–99.7%,88.4%–99.4%,98.2%,94.2%–100%,and 93.9%–100%,respectively.Notably,the vaccine strains exhibited high similarity in amino acid sequence,with only minor differences in antigenic epitopes compared to the Chinese endemic strains.This supports the potential application of the vaccine in preventing diseases caused by rotaviruses.展开更多
Rotaviruses, noroviruses, and astroviruses are responsible for gastroenteritis in children under 5 years old. The objective of our study was to estimate the evolution of prevalence of rotavirus, norovirus and astrovir...Rotaviruses, noroviruses, and astroviruses are responsible for gastroenteritis in children under 5 years old. The objective of our study was to estimate the evolution of prevalence of rotavirus, norovirus and astrovirus infections in children aged 0 to 5 years with gastroenteritis, after the introduction of rotavirus vaccines in Burkina Faso. This cross-sectional study was conducted between January and December 2023, collecting 100 stool samples from children with gastroenteritis at Saint Camille Hospital in Ouagadougou and the Charles De Gaulle University Paediatric Hospital. Noroviruses and astroviruses were detected using multiplex real-time PCR with a Sacace biotechnology detection kit. Data analysis was performed with Stata statistical software, version 16.0. The prevalence of norovirus infections was 14% and astrovirus infections were 9%. Rotavirus infections were found at prevalence of 15%. The age group most affected by norovirus and astrovirus infections was 0 - 12 months, with respective prevalence rates of 73.34% and 55.56%. The most frequently observed clinical signs in children infected with astrovirus were fever (77.78%), diarrhea (55.56%), and vomiting (44.44%). The introduction of rotavirus vaccines has reduced rotavirus-related infections. However, this has not significantly impacted the prevalence of norovirus and astrovirus infections in Burkina Faso.展开更多
Rotavirus diarrhea is a major worldwide cause of infantile gastroenteritis; however, the mechanism responsible for intestinal fluid loss remains unclear. Water transfer across the intestinal epithelial membrane seems ...Rotavirus diarrhea is a major worldwide cause of infantile gastroenteritis; however, the mechanism responsible for intestinal fluid loss remains unclear. Water transfer across the intestinal epithelial membrane seems to occur because of aquaporins(AQPs). Accumulating evidence indicates that alterations in AQPs may play an important role in pathogenesis. Here, we focus on changes in AQPs in a mouse model of rotavirus diarrhea. In the present study, 32 of 35 mice developed diarrhea and mild dehydration within 24 hours after infection with rotavirus strain SA11. Intestinal epithelial cells demonstrated cytoplasmic vacuolation, malaligned villi, and atrophy. AQP1 expression was significantly attenuated in the ileum and colon in comparison with controls; likewise, AQP4 and-8 protein expression were significantly decreased in the colon of rotavirus diarrhea-infected mice. In contrast, AQP3 protein expression was significantly increased in the colon of rotavirus-infected mice in comparison with controls. These results indicate that rotavirus diarrhea is associated with the downregulation of AQP1,-4, and-8 expression. Therefore, AQPs play an important role in rotavirus diarrhea.展开更多
Gastroenteritis is an infectious diarrhea that has been considered as an important cause of hospitalizations and death in children aged < 5 years, particularly in developing countries. Unsanitary water, contaminate...Gastroenteritis is an infectious diarrhea that has been considered as an important cause of hospitalizations and death in children aged < 5 years, particularly in developing countries. Unsanitary water, contaminated food, poor hygiene, and inadequate disposal of waste and feces are all risk factors for gastroenteritis, resulting in the higher incidence in developing countries. Gastroenteritis is generally caused by viral infections, among which rotavirus (RV) infections have been reported to be the most common, especially among young children aged < 5 years with acute gastroenteritis in Asia and Africa[1]. Other viruses associated with acute gastroenteritis include human Adenovirus (HAdV), Norovirus, Sapovirus (SaV), human Astrovirus (HAstV), and Aichi virus. Recent research has reported that adenovirus types 40 and 41, belonging to species F, cause gastroenteritis and were therefore termed as enteric adenoviruses. In addition, non-enteric HAdV species such as A, B, C, and D have been associated with diarrheal.展开更多
Background:Lentinan(LNT)may regulate many important physiological functions of human and animals.This study aimed to verify whether LNT administration could relieve diarrhea via improving gut immunity in rotavirus(RV)...Background:Lentinan(LNT)may regulate many important physiological functions of human and animals.This study aimed to verify whether LNT administration could relieve diarrhea via improving gut immunity in rotavirus(RV)-challenged weaned pigs.Methods:Twenty-eight weaned pigs were randomly fed 2 diets containing 0 or 84 mg/kg LNT product for 19 d(n=14).RV infection was executed on d 15.After extracting polysaccharides from LNT product,its major monosaccharides were analyzed.Then,LNT polysaccharide was used to administrate RV-infected IPEC-J2 cells.Results:Dietary LNT supplementation supported normal function of piglets even when infected with RV,as reflected by reduced growth performance loss and diarrhea prevalence,and maintained gut immunity(P<0.05).The polysaccharide was isolated from LNT product,which molecular weight was 5303 Da,and major monosaccharides included glucose,arabinose and galactose.In RV-infected IPEC-J2 cells,this polysaccharide significantly increased cell viability(P<0.05),and significantly increased anti-virus immunity via regulating pattern recognition receptors and host defense peptides(P<0.05).Conclusion:Those results suggest that LNT administration increases the piglets’resistance to RV-induced stress,likely by supporting intestinal immunity.展开更多
Rotavirus is an acute enteric pathogen in infants and children. We reported a rare case of a 6-mo-old infant with protein-loosing enteropathy (PLE) caused by rotavirus gastroenteritis, and evaluated the immunological ...Rotavirus is an acute enteric pathogen in infants and children. We reported a rare case of a 6-mo-old infant with protein-loosing enteropathy (PLE) caused by rotavirus gastroenteritis, and evaluated the immunological profile in peripheral blood lymphocytes. Laboratory examinations showed lymphopenia, hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia, and elevation of alpha-1-antitrypsin (α1-AT) clearance. Lymphocytes subpopulation study revealed the reversal of CD4+/CD8+ ratio with the selective decrease of CD4- positive lymphocytes. Moreover, the excessive increase of T cells producing IFN-gamma (IFN-γ) was found, which plays an important role in the protection against viral infection. The primary or secondary activation of immune system by rotavirus may influence structural integrity and vascular permeability, which may play a triggering role in protein-loosing enteropathy.展开更多
A randomized,double-blind,placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine(HRV)against rot...A randomized,double-blind,placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine(HRV)against rotavirus gastroenteritis(RVGE).A total of 6400 participants aged 6-12 weeks were enrolled and randomly assigned to either HRV(n?3200)or placebo(n?3200)group.All the subjects received three oral doses of vaccine four weeks apart.The vaccine efficacy(VE)against RVGE caused by rotavirus serotypes contained in HRV was evaluated from 14 days after three doses of administration up until the end of the second rotavirus season.VE against severe RVGE,VE against RVGE hospitalization caused by serotypes contained in HRV,and VE against RVGE,severe RVGE,and RVGE hospitalization caused by natural infection of any serotype of rotavirus were also investigated.All adverse events(AEs)were collected for 30 days after each dose.Serious AEs(SAEs)and intussusception cases were collected during the entire study.Our data showed that VE against RVGE caused by serotypes contained in HRV was 69.21%(95%CI:53.31-79.69).VE against severe RVGE and RVGE hospitalization caused by serotypes contained in HRV were 91.36%(95%CI:78.45-96.53)and 89.21%(95%CI:64.51-96.72)respectively.VE against RVGE,severe RVGE,and RVGE hospitalization caused by natural infection of any serotype of rotavirus were 62.88%(95%CI:49.11-72.92),85.51%(95%CI:72.74-92.30)and 83.68%(95%CI:61.34-93.11).Incidences of AEs from the first dose to one month post the third dose in HRV and placebo groups were comparable.There was no significant difference in incidences of SAEs in HRV and placebo groups.This study shows that this hexavalent reassortant rotavirus vaccine is an effective,well-tolerated,and safe vaccine for Chinese infants.展开更多
Rotaviruses are the single leading cause of life-threatening diarrhea affecting children under 5 years of age. Rotavirus entry into the host cell seems to occur by sequential interactions between virion proteins and v...Rotaviruses are the single leading cause of life-threatening diarrhea affecting children under 5 years of age. Rotavirus entry into the host cell seems to occur by sequential interactions between virion proteins and various cell surface molecules. The entry mechanisms seem to involve the contribution of cellular molecules having binding, chaperoning and oxido-reducing activities. It appears to be that the receptor usage and tropism of rotaviruses is determined by the species, cell line and rotavirus strain. Rotaviruses have evolved functions which can antagonize the host innate immune response, whereas are able to induce endoplasmic reticulum(ER) stress, oxidative stress and inflammatory signaling. A networking between ER stress, inflammation and oxidative stress is suggested, in which release of calcium from the ER increases the generation of mitochondrial reactive oxygen species(ROS) leading to toxic accumulation of ROS within ER and mitochondria. Sustained ER stress potentially stimulates inflammatory response through unfolded protein response pathways. However, the detailed characterization of the molecular mechanisms underpinning these rotavirus-induced stressful conditions is still lacking. The signaling events triggered by host recognition of virusassociated molecular patterns offers an opportunity for the development of novel therapeutic strategies aimed at interfering with rotavirus infection. The use of N-acetylcysteine, non-steroidal anti-inflammatory drugs and PPARγ agonists to inhibit rotavirus infection opens a new way for treating the rotavirus-induced diarrhea and complementing vaccines.展开更多
AIM: To investigate the effect of protein-energy malnutrition on intestinal barrier function during rotavirus enteritis in a piglet model.METHODS: Newborn piglets were allotted at day 4 of age to the following treatme...AIM: To investigate the effect of protein-energy malnutrition on intestinal barrier function during rotavirus enteritis in a piglet model.METHODS: Newborn piglets were allotted at day 4 of age to the following treatments:(1) full-strength formula(FSF)/noninfected;(2) FSF/rotavirus infected;(3) half-strength formula(HSF)/noninfected;or(4) HSF/rotavirus infected.After one day of adjustment to the feeding rates,pigs were infected with rotavirus and acute effects on growth and diarrhea were monitored for 3 d and jejunal samples were collected for Ussingchamber analyses.RESULTS: Piglets that were malnourished or infected had lower body weights on days 2 and 3 post-infection(P < 0.05).Three days post-infection,marked diarrhea and weight loss were accompanied by sharp reductions in villus height(59%) and lactase activity(91%) and increased crypt depth(21%) in infected compared with non-infected pigs(P < 0.05).Malnutrition also increased crypt depth(21%) compared to full-fed piglets.Villus:crypt ratio was reduced(67%) with viral infection.There was a trend for reduction in transepithelial electrical resistance with rotavirus infection and malnutrition(P = 0.1).3H-mannitol flux was significantly increased(50%;P < 0.001) in rotavirus-infected piglets compared to non-infected piglets,but there was no effect of nutritional status.Furthermore,rotavirus infection reduced localization of the tight junction protein,occludin,in the cell membrane and increased localization in the cytosol.CONCLUSION: Overall,malnutrition had no additive effects to rotavirus infection on intestinal barrier function at day 3 post-infection in a neonatal piglet model.展开更多
BACKGROUND: Biliary atresia, the etiology of which still remains unclear, occurs exclusively in newborns and most are infected with rotavirus. In this study, we aimed to investigate the histopathological patterns of d...BACKGROUND: Biliary atresia, the etiology of which still remains unclear, occurs exclusively in newborns and most are infected with rotavirus. In this study, we aimed to investigate the histopathological patterns of different kinds of rotavirus in the liver and biliary tract of neonatal mice and the expression of NF-kappa B in the liver and biliary tract of infected mice. METHODS: Twenty-three adult mice (8 were male and 15 female) were divided into 8 breeding pairs, and each pair (I male and 2 females) was housed in a cage in a laminar flow hood. Newborn mice, 24-48 hours old were randomly divided into A, B and C groups. The A and B groups were respectively inoculated with MMU18006 and SA11 rotavirus through the intraperitoneal route, while group C as blank control was only inoculated with culture medium. The liver was dissected after 5, 10, 15, 21 and 28 days; the weight of each mouse and the histopathological patterns in the liver were recorded. The expression of NF-kappa B in the liver and intrahepatic bile ducts was detected by immunohistochemical staining and the expression intensity was analyzed with a GT-2 imaging instrument. RESULTS: The average increase in weight of infected mice was significantly slower than that of the normal control, while the growth rate of group A (injected with MMU18006 rotavirus) was slower than that of group B (SA11 rotavirus). In infected mice, the acute and chronic inflammation of liver and intra- and extra-hepatic bile ducts was more significant in group A. Stenosis was found in most intrahepatic bile ducts, and sporadically in extrahepatic bile ducts. The expression of NF-kappa B in infected mice was dramatically higher than that of the normal control, while the expression in group A was higher than in group B. CONCLUSIONS: Significant damage to the liver and biliary tract of neonatal mice can be induced by inoculating MMU18006 rotavirus through the intraperitoneal route, which is very similar to the pathology of biliary atresia in the newborn human. Similar inoculation with SA11 rotavirus can only result in moderate impairment that disappears quickly. The difference of pathogenicity between the two rotaviruses may depend on their differing capacities to increase the expression of NF-kappa B in the liver and biliary tract.展开更多
Background:Rotavirus(RV)is a major pathogen that causes severe gastroenteritis in infants and young animals.Endoplasmic reticulum(ER)stress and subsequent apoptosis play pivotal role in virus infection.However,the pro...Background:Rotavirus(RV)is a major pathogen that causes severe gastroenteritis in infants and young animals.Endoplasmic reticulum(ER)stress and subsequent apoptosis play pivotal role in virus infection.However,the protective mechanisms of intestinal damage caused by RV are poorly defined,especially the molecular pathways related to enterocytes apoptosis.Thus,the aim of this study was to investigate the protective effect and mechanism of sodium butyrate(SB)on RV-induced apoptosis of IPEC-J2 cells.Results:The RV infection led to significant cell apoptosis,increased the expression levels of ER stress(ERS)markers,phosphorylated protein kinase-like ER kinase(PERK),eukaryotic initiation factor 2 alpha(eIF2α),caspase9,and caspase3.Blocking PERK pathway using specific inhibitor GSK subsequently reversed RV-induced cell apoptosis.The SB treatment significantly inhibited RV-induced ERS by decreasing the expression of glucose regulated protein 78(GRP78),PERK,and eIF2α.In addition,SB treatment restrained the ERS-mediated apoptotic pathway,as indicated by downregulation of C/EBP homologous protein(CHOP)mRNA level,as well as decreased cleaved caspase9 and caspase3 protein levels.Furthermore,siRNA-induced GPR109a knockdown significantly suppressed the protective effect of SB on RV-induced cell apoptosis.Conclusions:These results indicate that SB exerts protective effects against RV-induced cell apoptosis through inhibiting ERS mediated apoptosis by regulating PERK-eIF2αsignaling pathway via GPR109a,which provide new ideas for the prevention and control of RV.展开更多
AIM: to establish a new animal model for the research of human rotavirus(HRV) infection, its pathogenesis and immunity and evaluation of potential vaccines.METHODS: 5-d, 30-d and 60-d-old Chinese mini-pigs, Guizhou an...AIM: to establish a new animal model for the research of human rotavirus(HRV) infection, its pathogenesis and immunity and evaluation of potential vaccines.METHODS: 5-d, 30-d and 60-d-old Chinese mini-pigs, Guizhou and bamma, were inoculated with a single oral dose of attenuated strain Wa, G1, G3 of HRV, and PbS(control), respectively, and fecal samples of pigs from 0 to 7 d post infection(DPI) were collected individually. Enzyme linked immunosorbent assay was used to detect HRV antigen in feces. the HRV was tested by real-time PCR(Rt-PCR). the sections of the intestinal tissue were stained with hematoxylin and eosin to observe the morphologic variation by microscopy. Immunofluorescence was used to determine the HRV in intestinal tissue. HRV particles in cells of the ileum were observed by electron micrography.RESULTS: When inoculated with HRV, mini-pigs younger than 30 d developed diarrhea in an agedependent manner and shed HRV antigen of the sameinoculum, as demonstrated by Rt- PCR.Histopathological changes were observed in HRV inoculated mini-pigs including small intestinal cell tumefaction and necrosis. HRV that was distributed in the small intestine was restricted to the top part of the villi on the internal wall of the ileum, which was observed by immunofluorescence and transmission electron microscopy. Virus particles were observed in Golgi like follicles in HRV-infected neonatal minipigs. Guizhou mini-pigs were more sensitive to HRV than bamma with respect to RV antigen shedding and clinical diarrhea.CONCLUSION: these results indicate that we have established a mini-pig model of HRV induced diarrhea. Our findings are useful for the understanding of the pathogenic mechanisms of HRV infection.展开更多
The effects of free chlorine disinfection of tap water and wastewater effluents on the infectivity, gene integrity and surface antigens of rotaviruses were evaluated by a bench-scale chlorine disinfection experiments....The effects of free chlorine disinfection of tap water and wastewater effluents on the infectivity, gene integrity and surface antigens of rotaviruses were evaluated by a bench-scale chlorine disinfection experiments. Plaque assays, integrated cell culture-quantitative RT- PCR （ICC-RT-qPCR）, RT-qPCR, and enzyme-linked immunosorbent assays （ELISA）, respectively, were used to assess the influence of the disinfectant on virus infectivity as well as genetic and antigenic integrity of simian rotavirus SA11 as a surrogate for human rotaviruses. The ICC-RT-qPCR was able to detect rotaviruses survival from chlorine disinfection at chlorine dose up to 20 mg/L （60 min contact）, which suggested a required chlorine dose of 5 folds （from 1 to 5 mg/L） higher than that indicated by the plaque assay to achieve 1.8 log10 reductions in tap water with 60 rain exposing. The VP7 gene was more resistant than the infectivity and existed at chlorine dose up to 20 mg/L （60 min contact）, while the antigencity was undetectable with chlorine dose more than 5 mg/L （60 min contact）. The water quality also impacted the inactivation efficiencies, and rotaviruses have a relatively higher resistant in secondary effluents than in the tap water under the same chlorine disinfection treatments. This study indicated that rotaviruses have a higher infectivity, gene and antigencity resistance to chlorine than that previously indicated by plaque assay only, which seemed to underestimate the resistance of rotaviruses to chlorine and the risk of rotaviruses in environments. Present results also suggested that re-evaluation of resistance of other waterborne viruses after disinfections by more sensitive infectivity detection method （such as ICC-RT-qPCR） may be necessary, to determine the adequate disinfectant doses required for the inactivation of waterborne viruses.展开更多
AIM:To study the effects of live and dead Lactobacillus rhamnosus GG(GG) on rotavirus infection in a neonatal rat model.METHODS:At the age of 2 d,suckling Lewis rat pups were supplemented with either live or dead GG a...AIM:To study the effects of live and dead Lactobacillus rhamnosus GG(GG) on rotavirus infection in a neonatal rat model.METHODS:At the age of 2 d,suckling Lewis rat pups were supplemented with either live or dead GG and the treatment was continued daily throughout the experi-ment.At the age of 5 and 6 d the pups received oral rotavirus(RV) SA-11 strain.The pups were sacrificed at the age of 7 or 8 d by decapitation.The gastrointestinal tract was removed and macroscopic observations were done.The consistency of feces in the colon was classified using a four-tier system.RV was detected from the plasma,small intestine,colon and feces by real-time quantitative polymerase chain reaction(PCR).RESULTS:In this neonatal rat model,RV induced a mild-to-moderate diarrhea in all except one pup of the RV-inoculated rats.RV moderately reduced body weight development from day 6 onwards.On day 7,after 2 d of RV infection,live and dead GG groups gained significantly more weight than the RV group without probiotics [36%(P = 0.001) and 28%(P = 0.031),respectively].In addition,when compared with the RV control group,both live and dead GG reduced the weight ratio of colon/animal body weight to the same level as in the healthy control group,with reductions of 22%(P = 0.002) and 28%(P < 0.001),respectively.Diarrhea increased moderately in both GG groups.However,the diarrhea incidence and severity in the GG groups were not statistically significantly different as compared with the RV control group.Moreover,observed diarrhea did not provoke weight loss or death.The RV control group had the largest amount of RV PCR-positive samples among the RV-infected groups,and the live GG group had the smallest amount.Rats receiving live GG had significantly less RV in the colon(P = 0.027) when compared with the RV control group.Live GG was also more effective over dead GG in reducing the quantity of RV from plasma(P = 0.047).CONCLUSION:Both live and dead GG have beneficial effects in RV infection.GG may increase RV clearance from the body and reduce colon swelling.展开更多
基金supported by the National Key Laboratory of Agricultural Microbiology(AML2023A02)the Fundamental Research Funds for the Central Universities(2662023DKPY004).
文摘Rotavirus infections cause severe gastroenteritis and dehydration in young children and animals worldwide,leading to high rates of morbidity and mortality,predominantly in low-and middleincome countries.In the past decade,substantial progress has been made in the development and implementation of rotavirus vaccines,which have been essential in alleviating the global burden of this disease,not only in human being but also in livestock species like calves and piglets,where these infections can cause significant economic losses.By synthesizing the latest research and real-world evidence,this review article is designated to provide deep insights into the current state of rotavirus vaccine technology and its global implementation as well as the application of rotavirus vaccines in veterinary settings and their importance in controlling zoonotic transmission and maintaining food security.
基金supported by the National Natural Science Foundation of China(Grant no.32402927).
文摘As an emerging genotype,the G9 genotype rotaviruses(RVs)are widespread among humans and pigs,and have been reported in many countries and regions in the recent years.Moreover,porcine G9 strains could cross the interspecies barrier to infect human.To investigate the epidemic trends of porcine G9 strains as well as the cross-immunoreactivity among different isolates,an epidemiological investigation about porcine G9 genotype RVs(PoRVs)was performed during the period 2020-2023 in multiple provinces of China.A total of nine representative strains were identified.The phylogenetic analysis based on viral VP7 gene showed that these strains mainly clustered with lineages Ⅲ and Ⅵ,which revealed the predominant G9 PoRVs in China.Moreover,a new lineage,lineage Ⅶ,was identified,and strains of this lineage were found to be circulating in Guangdong and Taiwan.Except lineages Ⅰ and Ⅳ,some isolates from other lineages could co-circulate in pigs and humans.Three G9 strains,namely 923H,923E,and 923X,which belonged to the largest sub-lineage Ⅲ,were isolated.Then,the significant cross-reactivity was observed among strains of the same or different lineages.This study is the first to systematically investigate the genetic and immunogenetic characteristics of porcine G9 genotype rotavirus in China,as well as the potential cross-species transmission between pigs and humans,providing a valuable direction for the effective prevention of porcine rotavirus.
文摘The original version of Figure 2 contained the following inaccuracies:Rotarix was incorrectly shown as a 3-dose vaccine instead of a 2-dose vaccine;RotaTeq and Rotasiil were incorrectly shown as 2-dose vaccines instead of 3-dose vaccines;Polyvac was incorrectly shown as a 3-dose vaccine instead of a 2-dose regimen;and the LLR vaccine should have been indicated as a single primary dose followed by annual boosters between 2 months and 3 years of age.
文摘BACKGROUND Rotavirus(RV),a primary cause of diarrhea-related mortality in 2021,has been shown to damage intestinal epithelial cells while upregulating intestinal stem cells(ISCs)activities.ISCs within the crypt niche drive the continuous self-renewal of intestinal epithelium,preserving its barrier functions.Paneth cells secrete antimicrobial peptide and signaling molecules within the intestine crypt,thereby playing a crucial role in intestinal immune defense and providing ISCs functional support.However,the regulatory function of Paneth cells under pathological conditions,such as RV infection,remains unclear.AIM To determine the impact of RV infection on Paneth cells and how Paneth cells regulate ISCs during intestinal injury repair.METHODS We constructed a reference genome for the RV enteric cytopathogenic human orphan virus strain and reanalyzed published single-cell RNA sequencing data to investigate Paneth cell responses to RV-induced intestinal injury.We derived Paneth-ISC communication networks using CellChat,tracked ISC differentiation with pseudotime analysis,and validated our findings in leucine-rich repeat-containing G protein-coupled receptor 5-enhanced green fluorescent protein-internal ribosomal entry site-Cre recombinase estrogen receptor variant 2 mice and organoids via immunofluorescence,flow cytometry,and reverse transcription quantitative polymerase chain reaction.RESULTS We found that RV directly infects Paneth cells,leading to a reduction in mature Paneth cells and an increase in kallikrein 1-high immature Paneth cells.Paneth-ISC communication was significantly enhanced.In particular,the bone morphogenic protein 7(BMP7)-activin A receptor type 2B/BMP receptor type 1A-Smad pathway was upregulated post-infection,suggesting that Paneth cells suppress excessive ISC proliferation.Functional validation confirmed activation of this pathway.CONCLUSION Paneth cells regulate ISC proliferation during RV infection by activating BMP7 signaling,limiting excessive stem cell expansion and preserving crypt homeostasis for effective epithelial repair.
基金the Study on Vaccine Application Evaluation Strategies and Capacity Building (INV-006373)the National Key R&D Program of China(2024YFC2310604)
文摘Objective The objective of our study was to evaluate the vaccine effectiveness(VE)of the pentavalent rotavirus vaccine(RV5)among<5-year-old children in three provinces of China during 2020-2024 via a propensity score-matched test-negative case-control study.Methods Electronic health records and immunization information systems were used to obtain data on acute gastroenteritis(AGE)cases tested for rotavirus(RV)infection.RV-positive cases were propensity score matched with RV-negative controls for age,visit month,and province.Results The study included 27,472 children with AGE aged 8 weeks to 4 years at the time of AGE diagnosis;7.98%(2,192)were RV-positive.The VE(95%confidence interval,CI)of 1-2 and 3 doses of RV5 against any medically attended RV infection(inpatient or outpatient)was 57.6%(39.8%,70.2%)and 67.2%(60.3%,72.9%),respectively.Among children who received the 3rd dose before turning 5 months of age,3-dose VE decreased from 70.4%(53.9%,81.1%)(<5 months since the 3rd dose)to 63.0%(49.1%,73.0%)(≥1 year since the 3rd dose).The three-dose VE rate was 69.4%(41.3%,84.0%)for RVGE hospitalization and 57.5%(38.9%,70.5%)for outpatient-only medically attended RVGE.Conclusion Three-dose RV5 VE against rotavirus gastroenteritis(RVGE)in children aged<5 years was higher than 1-2-dose VE.Three-dose VE decreased with time since the 3rd dose in children who received the 3rd dose before turning five months of age,but remained above 60%for at least one year.VE was higher for RVGE hospitalizations than for medically attended outpatient visits.
基金RVA G/[P]-genotypes was at the expense of the Russian Science Foundation(Grant No.16-15-10332)
文摘Enteric viruses are the most common cause of acute gastroenteritis （AGE） in young children and a significant public health problem globally. Hospital admissions of children under 5 years of age with diarrhea are primarily associated with group A rotavirus （RVA） infection. In this retrospective study, the population structure of viruses linked to AGE etiology in young children hospitalized with AGE in Moscow was evaluated, and molecular characterization of RYA strains was performed. Fecal specimens were collected from children under 5 years old hospitalized with AGE between 2009 and 2014 in Moscow, Russia. Multiplex real-time reverse transcription PCR was used to detect enteric viruses and for G/[P]-genotyping of isolated RVAs. Sequencing of RVA VP7 and VP4 cDNA fragments was used to validate the data obtained by PCR- genotyping. The main causes for hospitalization of children with AGE were RVA （40.1%）, followed by noroviruses （11.4%）, while adenoviruses, astroviruses, sapoviruses, enteroviruses, and orthoreoviruses were detected in 4.7%, 1.9%, 1.4%, 1.2%, and 0.2% of samples tested, respectively. Nosocomial infections, predominantly associated with RVAs and noroviruses, were detected in 24.8% of cases and occurred significantly more frequently in younger infants. The predominant RVA genotype was G4P[8], detected in 38.7% of RVA-positive cases, whereas genotypes G1P[8], G9P[8], G3P[8], and G2P[4] were found in 11.8%, 6.6%, 4.2%, and 3.3% of cases, respectively. Together, the presence of circulating RVA strains with rare VP7 and VP4 gene variants （G6 and P[9]） highlights the need to conduct continuous epidemiological monitoring of RVA infection.
基金the National Health Committee of the People's Republic of China(grant number:2019ZX09302059).
文摘The oral hexavalent live human-bovine reassortant rotavirus vaccine(RV6)developed by Wuhan Institute of Biological Products Co.,Ltd(WIBP)has finished a randomized,placebo-controlled phase III clinical trial in four provinces of China in 2021.The trail demonstrated that RV6 has a high vaccine efficacy against the prevalent strains and is safe for use in infants.During the phase III clinical trial(2019–2021),200 rotavirus-positive fecal samples from children with RV gastroenteritis(RVGE)were further studied.Using reverse transcription-polymerase chain reaction and high-throughput sequencing,VP7 and VP4 sequences were obtained and their genetic characteristics,as well as the differences in antigenic epitopes of VP7,were analyzed in detail.Seven rotavirus genotypes were identified.The predominant rotavirus genotype was G9P[8](77.0%),followed by prevalent strains G8P[8](8.0%),G3P[8](3.5%),G3P[9](1.5%),G1P[8](1.0%),G2P[4](1.0%),and G4P[6](1.0%).The amino acid sequence identities of G1,G2,G3,G4,G8,and G9 genotypes of isolates compared to the vaccine strains were 98.8%,98.2%–99.7%,88.4%–99.4%,98.2%,94.2%–100%,and 93.9%–100%,respectively.Notably,the vaccine strains exhibited high similarity in amino acid sequence,with only minor differences in antigenic epitopes compared to the Chinese endemic strains.This supports the potential application of the vaccine in preventing diseases caused by rotaviruses.
文摘Rotaviruses, noroviruses, and astroviruses are responsible for gastroenteritis in children under 5 years old. The objective of our study was to estimate the evolution of prevalence of rotavirus, norovirus and astrovirus infections in children aged 0 to 5 years with gastroenteritis, after the introduction of rotavirus vaccines in Burkina Faso. This cross-sectional study was conducted between January and December 2023, collecting 100 stool samples from children with gastroenteritis at Saint Camille Hospital in Ouagadougou and the Charles De Gaulle University Paediatric Hospital. Noroviruses and astroviruses were detected using multiplex real-time PCR with a Sacace biotechnology detection kit. Data analysis was performed with Stata statistical software, version 16.0. The prevalence of norovirus infections was 14% and astrovirus infections were 9%. Rotavirus infections were found at prevalence of 15%. The age group most affected by norovirus and astrovirus infections was 0 - 12 months, with respective prevalence rates of 73.34% and 55.56%. The most frequently observed clinical signs in children infected with astrovirus were fever (77.78%), diarrhea (55.56%), and vomiting (44.44%). The introduction of rotavirus vaccines has reduced rotavirus-related infections. However, this has not significantly impacted the prevalence of norovirus and astrovirus infections in Burkina Faso.
基金supported by funding from Guangdong Natural Science Foundation (grants:S2012010009211,S2012010009538)Key Specialty Projects of Guangzhou Board of Health (grant:20121A021014)
文摘Rotavirus diarrhea is a major worldwide cause of infantile gastroenteritis; however, the mechanism responsible for intestinal fluid loss remains unclear. Water transfer across the intestinal epithelial membrane seems to occur because of aquaporins(AQPs). Accumulating evidence indicates that alterations in AQPs may play an important role in pathogenesis. Here, we focus on changes in AQPs in a mouse model of rotavirus diarrhea. In the present study, 32 of 35 mice developed diarrhea and mild dehydration within 24 hours after infection with rotavirus strain SA11. Intestinal epithelial cells demonstrated cytoplasmic vacuolation, malaligned villi, and atrophy. AQP1 expression was significantly attenuated in the ileum and colon in comparison with controls; likewise, AQP4 and-8 protein expression were significantly decreased in the colon of rotavirus diarrhea-infected mice. In contrast, AQP3 protein expression was significantly increased in the colon of rotavirus-infected mice in comparison with controls. These results indicate that rotavirus diarrhea is associated with the downregulation of AQP1,-4, and-8 expression. Therefore, AQPs play an important role in rotavirus diarrhea.
基金supported by major project granted by the Science and Technology Ministry of China [grant no.2017ZX10104001]
文摘Gastroenteritis is an infectious diarrhea that has been considered as an important cause of hospitalizations and death in children aged < 5 years, particularly in developing countries. Unsanitary water, contaminated food, poor hygiene, and inadequate disposal of waste and feces are all risk factors for gastroenteritis, resulting in the higher incidence in developing countries. Gastroenteritis is generally caused by viral infections, among which rotavirus (RV) infections have been reported to be the most common, especially among young children aged < 5 years with acute gastroenteritis in Asia and Africa[1]. Other viruses associated with acute gastroenteritis include human Adenovirus (HAdV), Norovirus, Sapovirus (SaV), human Astrovirus (HAstV), and Aichi virus. Recent research has reported that adenovirus types 40 and 41, belonging to species F, cause gastroenteritis and were therefore termed as enteric adenoviruses. In addition, non-enteric HAdV species such as A, B, C, and D have been associated with diarrheal.
基金This study was financially supported by the grant from the earmarked fund for the China Agriculture Research System(CARS-35)the fund from the Project of SAU-Adisseo Centre of Research on Nutrition and Healththe fund from Agricultural Science and Technology Achievement Transformation Fund Project of Sichuan Province(2016NYZ0052 and 20NZZH0057).
文摘Background:Lentinan(LNT)may regulate many important physiological functions of human and animals.This study aimed to verify whether LNT administration could relieve diarrhea via improving gut immunity in rotavirus(RV)-challenged weaned pigs.Methods:Twenty-eight weaned pigs were randomly fed 2 diets containing 0 or 84 mg/kg LNT product for 19 d(n=14).RV infection was executed on d 15.After extracting polysaccharides from LNT product,its major monosaccharides were analyzed.Then,LNT polysaccharide was used to administrate RV-infected IPEC-J2 cells.Results:Dietary LNT supplementation supported normal function of piglets even when infected with RV,as reflected by reduced growth performance loss and diarrhea prevalence,and maintained gut immunity(P<0.05).The polysaccharide was isolated from LNT product,which molecular weight was 5303 Da,and major monosaccharides included glucose,arabinose and galactose.In RV-infected IPEC-J2 cells,this polysaccharide significantly increased cell viability(P<0.05),and significantly increased anti-virus immunity via regulating pattern recognition receptors and host defense peptides(P<0.05).Conclusion:Those results suggest that LNT administration increases the piglets’resistance to RV-induced stress,likely by supporting intestinal immunity.
文摘Rotavirus is an acute enteric pathogen in infants and children. We reported a rare case of a 6-mo-old infant with protein-loosing enteropathy (PLE) caused by rotavirus gastroenteritis, and evaluated the immunological profile in peripheral blood lymphocytes. Laboratory examinations showed lymphopenia, hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia, and elevation of alpha-1-antitrypsin (α1-AT) clearance. Lymphocytes subpopulation study revealed the reversal of CD4+/CD8+ ratio with the selective decrease of CD4- positive lymphocytes. Moreover, the excessive increase of T cells producing IFN-gamma (IFN-γ) was found, which plays an important role in the protection against viral infection. The primary or secondary activation of immune system by rotavirus may influence structural integrity and vascular permeability, which may play a triggering role in protein-loosing enteropathy.
基金supported by National Health Commission of the People’s Republic of China (grant number:2019ZX09302059)sponsored and funded by Wuhan Institute of Biological Products Co.,Ltd.,Hubei,China
文摘A randomized,double-blind,placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine(HRV)against rotavirus gastroenteritis(RVGE).A total of 6400 participants aged 6-12 weeks were enrolled and randomly assigned to either HRV(n?3200)or placebo(n?3200)group.All the subjects received three oral doses of vaccine four weeks apart.The vaccine efficacy(VE)against RVGE caused by rotavirus serotypes contained in HRV was evaluated from 14 days after three doses of administration up until the end of the second rotavirus season.VE against severe RVGE,VE against RVGE hospitalization caused by serotypes contained in HRV,and VE against RVGE,severe RVGE,and RVGE hospitalization caused by natural infection of any serotype of rotavirus were also investigated.All adverse events(AEs)were collected for 30 days after each dose.Serious AEs(SAEs)and intussusception cases were collected during the entire study.Our data showed that VE against RVGE caused by serotypes contained in HRV was 69.21%(95%CI:53.31-79.69).VE against severe RVGE and RVGE hospitalization caused by serotypes contained in HRV were 91.36%(95%CI:78.45-96.53)and 89.21%(95%CI:64.51-96.72)respectively.VE against RVGE,severe RVGE,and RVGE hospitalization caused by natural infection of any serotype of rotavirus were 62.88%(95%CI:49.11-72.92),85.51%(95%CI:72.74-92.30)and 83.68%(95%CI:61.34-93.11).Incidences of AEs from the first dose to one month post the third dose in HRV and placebo groups were comparable.There was no significant difference in incidences of SAEs in HRV and placebo groups.This study shows that this hexavalent reassortant rotavirus vaccine is an effective,well-tolerated,and safe vaccine for Chinese infants.
文摘Rotaviruses are the single leading cause of life-threatening diarrhea affecting children under 5 years of age. Rotavirus entry into the host cell seems to occur by sequential interactions between virion proteins and various cell surface molecules. The entry mechanisms seem to involve the contribution of cellular molecules having binding, chaperoning and oxido-reducing activities. It appears to be that the receptor usage and tropism of rotaviruses is determined by the species, cell line and rotavirus strain. Rotaviruses have evolved functions which can antagonize the host innate immune response, whereas are able to induce endoplasmic reticulum(ER) stress, oxidative stress and inflammatory signaling. A networking between ER stress, inflammation and oxidative stress is suggested, in which release of calcium from the ER increases the generation of mitochondrial reactive oxygen species(ROS) leading to toxic accumulation of ROS within ER and mitochondria. Sustained ER stress potentially stimulates inflammatory response through unfolded protein response pathways. However, the detailed characterization of the molecular mechanisms underpinning these rotavirus-induced stressful conditions is still lacking. The signaling events triggered by host recognition of virusassociated molecular patterns offers an opportunity for the development of novel therapeutic strategies aimed at interfering with rotavirus infection. The use of N-acetylcysteine, non-steroidal anti-inflammatory drugs and PPARγ agonists to inhibit rotavirus infection opens a new way for treating the rotavirus-induced diarrhea and complementing vaccines.
基金Supported by Cooperative State Research,Education and Extension Service,USDA-National Research Initiative,No.2005-35200-16174the North Carolina Agriculture Research Service
文摘AIM: To investigate the effect of protein-energy malnutrition on intestinal barrier function during rotavirus enteritis in a piglet model.METHODS: Newborn piglets were allotted at day 4 of age to the following treatments:(1) full-strength formula(FSF)/noninfected;(2) FSF/rotavirus infected;(3) half-strength formula(HSF)/noninfected;or(4) HSF/rotavirus infected.After one day of adjustment to the feeding rates,pigs were infected with rotavirus and acute effects on growth and diarrhea were monitored for 3 d and jejunal samples were collected for Ussingchamber analyses.RESULTS: Piglets that were malnourished or infected had lower body weights on days 2 and 3 post-infection(P < 0.05).Three days post-infection,marked diarrhea and weight loss were accompanied by sharp reductions in villus height(59%) and lactase activity(91%) and increased crypt depth(21%) in infected compared with non-infected pigs(P < 0.05).Malnutrition also increased crypt depth(21%) compared to full-fed piglets.Villus:crypt ratio was reduced(67%) with viral infection.There was a trend for reduction in transepithelial electrical resistance with rotavirus infection and malnutrition(P = 0.1).3H-mannitol flux was significantly increased(50%;P < 0.001) in rotavirus-infected piglets compared to non-infected piglets,but there was no effect of nutritional status.Furthermore,rotavirus infection reduced localization of the tight junction protein,occludin,in the cell membrane and increased localization in the cytosol.CONCLUSION: Overall,malnutrition had no additive effects to rotavirus infection on intestinal barrier function at day 3 post-infection in a neonatal piglet model.
文摘BACKGROUND: Biliary atresia, the etiology of which still remains unclear, occurs exclusively in newborns and most are infected with rotavirus. In this study, we aimed to investigate the histopathological patterns of different kinds of rotavirus in the liver and biliary tract of neonatal mice and the expression of NF-kappa B in the liver and biliary tract of infected mice. METHODS: Twenty-three adult mice (8 were male and 15 female) were divided into 8 breeding pairs, and each pair (I male and 2 females) was housed in a cage in a laminar flow hood. Newborn mice, 24-48 hours old were randomly divided into A, B and C groups. The A and B groups were respectively inoculated with MMU18006 and SA11 rotavirus through the intraperitoneal route, while group C as blank control was only inoculated with culture medium. The liver was dissected after 5, 10, 15, 21 and 28 days; the weight of each mouse and the histopathological patterns in the liver were recorded. The expression of NF-kappa B in the liver and intrahepatic bile ducts was detected by immunohistochemical staining and the expression intensity was analyzed with a GT-2 imaging instrument. RESULTS: The average increase in weight of infected mice was significantly slower than that of the normal control, while the growth rate of group A (injected with MMU18006 rotavirus) was slower than that of group B (SA11 rotavirus). In infected mice, the acute and chronic inflammation of liver and intra- and extra-hepatic bile ducts was more significant in group A. Stenosis was found in most intrahepatic bile ducts, and sporadically in extrahepatic bile ducts. The expression of NF-kappa B in infected mice was dramatically higher than that of the normal control, while the expression in group A was higher than in group B. CONCLUSIONS: Significant damage to the liver and biliary tract of neonatal mice can be induced by inoculating MMU18006 rotavirus through the intraperitoneal route, which is very similar to the pathology of biliary atresia in the newborn human. Similar inoculation with SA11 rotavirus can only result in moderate impairment that disappears quickly. The difference of pathogenicity between the two rotaviruses may depend on their differing capacities to increase the expression of NF-kappa B in the liver and biliary tract.
基金supported by Key Program for the National Key Research&Development Program of China(2018YFD0501004)the National Natural Science Foundation of China(31730091)the Sichuan Science and Technology Support Program(2020YFN0147).
文摘Background:Rotavirus(RV)is a major pathogen that causes severe gastroenteritis in infants and young animals.Endoplasmic reticulum(ER)stress and subsequent apoptosis play pivotal role in virus infection.However,the protective mechanisms of intestinal damage caused by RV are poorly defined,especially the molecular pathways related to enterocytes apoptosis.Thus,the aim of this study was to investigate the protective effect and mechanism of sodium butyrate(SB)on RV-induced apoptosis of IPEC-J2 cells.Results:The RV infection led to significant cell apoptosis,increased the expression levels of ER stress(ERS)markers,phosphorylated protein kinase-like ER kinase(PERK),eukaryotic initiation factor 2 alpha(eIF2α),caspase9,and caspase3.Blocking PERK pathway using specific inhibitor GSK subsequently reversed RV-induced cell apoptosis.The SB treatment significantly inhibited RV-induced ERS by decreasing the expression of glucose regulated protein 78(GRP78),PERK,and eIF2α.In addition,SB treatment restrained the ERS-mediated apoptotic pathway,as indicated by downregulation of C/EBP homologous protein(CHOP)mRNA level,as well as decreased cleaved caspase9 and caspase3 protein levels.Furthermore,siRNA-induced GPR109a knockdown significantly suppressed the protective effect of SB on RV-induced cell apoptosis.Conclusions:These results indicate that SB exerts protective effects against RV-induced cell apoptosis through inhibiting ERS mediated apoptosis by regulating PERK-eIF2αsignaling pathway via GPR109a,which provide new ideas for the prevention and control of RV.
基金Supported by National Natural Science Foundation of China,No.30400402 and No.30571708
文摘AIM: to establish a new animal model for the research of human rotavirus(HRV) infection, its pathogenesis and immunity and evaluation of potential vaccines.METHODS: 5-d, 30-d and 60-d-old Chinese mini-pigs, Guizhou and bamma, were inoculated with a single oral dose of attenuated strain Wa, G1, G3 of HRV, and PbS(control), respectively, and fecal samples of pigs from 0 to 7 d post infection(DPI) were collected individually. Enzyme linked immunosorbent assay was used to detect HRV antigen in feces. the HRV was tested by real-time PCR(Rt-PCR). the sections of the intestinal tissue were stained with hematoxylin and eosin to observe the morphologic variation by microscopy. Immunofluorescence was used to determine the HRV in intestinal tissue. HRV particles in cells of the ileum were observed by electron micrography.RESULTS: When inoculated with HRV, mini-pigs younger than 30 d developed diarrhea in an agedependent manner and shed HRV antigen of the sameinoculum, as demonstrated by Rt- PCR.Histopathological changes were observed in HRV inoculated mini-pigs including small intestinal cell tumefaction and necrosis. HRV that was distributed in the small intestine was restricted to the top part of the villi on the internal wall of the ileum, which was observed by immunofluorescence and transmission electron microscopy. Virus particles were observed in Golgi like follicles in HRV-infected neonatal minipigs. Guizhou mini-pigs were more sensitive to HRV than bamma with respect to RV antigen shedding and clinical diarrhea.CONCLUSION: these results indicate that we have established a mini-pig model of HRV induced diarrhea. Our findings are useful for the understanding of the pathogenic mechanisms of HRV infection.
基金supported by the Special Fund of State Key Joint Laboratory of Environment Simulation and Pollution Control of China (No. 10Y04ESPCT)the National Natural Science Fundation of China (No. 51178242)the Major Science and Technology Program for Water Pollution Control and Treatment of China (No. 2008ZX07313-007)
文摘The effects of free chlorine disinfection of tap water and wastewater effluents on the infectivity, gene integrity and surface antigens of rotaviruses were evaluated by a bench-scale chlorine disinfection experiments. Plaque assays, integrated cell culture-quantitative RT- PCR （ICC-RT-qPCR）, RT-qPCR, and enzyme-linked immunosorbent assays （ELISA）, respectively, were used to assess the influence of the disinfectant on virus infectivity as well as genetic and antigenic integrity of simian rotavirus SA11 as a surrogate for human rotaviruses. The ICC-RT-qPCR was able to detect rotaviruses survival from chlorine disinfection at chlorine dose up to 20 mg/L （60 min contact）, which suggested a required chlorine dose of 5 folds （from 1 to 5 mg/L） higher than that indicated by the plaque assay to achieve 1.8 log10 reductions in tap water with 60 rain exposing. The VP7 gene was more resistant than the infectivity and existed at chlorine dose up to 20 mg/L （60 min contact）, while the antigencity was undetectable with chlorine dose more than 5 mg/L （60 min contact）. The water quality also impacted the inactivation efficiencies, and rotaviruses have a relatively higher resistant in secondary effluents than in the tap water under the same chlorine disinfection treatments. This study indicated that rotaviruses have a higher infectivity, gene and antigencity resistance to chlorine than that previously indicated by plaque assay only, which seemed to underestimate the resistance of rotaviruses to chlorine and the risk of rotaviruses in environments. Present results also suggested that re-evaluation of resistance of other waterborne viruses after disinfections by more sensitive infectivity detection method （such as ICC-RT-qPCR） may be necessary, to determine the adequate disinfectant doses required for the inactivation of waterborne viruses.
基金Supported by Valio Ltd and the Finnish Funding Agency of Technology and InnovationThe Foundation for Nutrition Research has financially contributed to Liisa Lehtoranta’s doctoral studies
文摘AIM:To study the effects of live and dead Lactobacillus rhamnosus GG(GG) on rotavirus infection in a neonatal rat model.METHODS:At the age of 2 d,suckling Lewis rat pups were supplemented with either live or dead GG and the treatment was continued daily throughout the experi-ment.At the age of 5 and 6 d the pups received oral rotavirus(RV) SA-11 strain.The pups were sacrificed at the age of 7 or 8 d by decapitation.The gastrointestinal tract was removed and macroscopic observations were done.The consistency of feces in the colon was classified using a four-tier system.RV was detected from the plasma,small intestine,colon and feces by real-time quantitative polymerase chain reaction(PCR).RESULTS:In this neonatal rat model,RV induced a mild-to-moderate diarrhea in all except one pup of the RV-inoculated rats.RV moderately reduced body weight development from day 6 onwards.On day 7,after 2 d of RV infection,live and dead GG groups gained significantly more weight than the RV group without probiotics [36%(P = 0.001) and 28%(P = 0.031),respectively].In addition,when compared with the RV control group,both live and dead GG reduced the weight ratio of colon/animal body weight to the same level as in the healthy control group,with reductions of 22%(P = 0.002) and 28%(P < 0.001),respectively.Diarrhea increased moderately in both GG groups.However,the diarrhea incidence and severity in the GG groups were not statistically significantly different as compared with the RV control group.Moreover,observed diarrhea did not provoke weight loss or death.The RV control group had the largest amount of RV PCR-positive samples among the RV-infected groups,and the live GG group had the smallest amount.Rats receiving live GG had significantly less RV in the colon(P = 0.027) when compared with the RV control group.Live GG was also more effective over dead GG in reducing the quantity of RV from plasma(P = 0.047).CONCLUSION:Both live and dead GG have beneficial effects in RV infection.GG may increase RV clearance from the body and reduce colon swelling.
