Periodontitis is the inflammation of the supporting structures around the dentition.Several microbial agents,mostly bacteria,have been identified as causative factors for periodontal disease.On the other hand,oral cav...Periodontitis is the inflammation of the supporting structures around the dentition.Several microbial agents,mostly bacteria,have been identified as causative factors for periodontal disease.On the other hand,oral cavity is a rich reservoir for viruses since it contains a wide variety of cell types that can be targeted by viruses.Traditionally,the focus of research about the oral flora has been on bacteria because the most widespread oral diseases,like periodontitis and dental caries,are outcomes of bacterial infection.However,recently and especially after the emergence of coronavirus disease 2019,there is a growing tendency toward including viruses also into the scope of oral microbiome investigations.The global high prevalence of periodontitis and viral infections may point out to a concomitant or synergistic effect between the two.Although the exact nature of the mechanism still is not clearly understood,this could be speculated through the manipulation of the immune system by viruses;hence facilitating the furthermore colonization of the oral tissues by bacteria.This review provides an extensive and detailed update on the role of the most common viruses including herpes family(herpes simplex,varicella-zoster,Epstein-Barr,cytomegalovirus),Human papillomaviruses,Human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2 in the initiation,progression and prognosis of periodontitis.展开更多
BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investi...BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.展开更多
Dear Editor,For the past few decades,mosquito-borne orthoflaviviruses,such as dengue virus,Zika virus,and West Nile virus(WNV),have posed significant threats to global public health.The Orthoflavivirus genus comprises...Dear Editor,For the past few decades,mosquito-borne orthoflaviviruses,such as dengue virus,Zika virus,and West Nile virus(WNV),have posed significant threats to global public health.The Orthoflavivirus genus comprises more than 70 viruses,many of which are responsible for a wide range of diseases in humans and animals,including febrile illnesses,encephalitis,and hemorrhagic febrile illness.These viruses are associated with approximately 400 million infections and 100 million symptomatic cases worldwide each year(Van Leur et al.,2021).Among them,Usutu virus(USUV)is an emerging pathogen classified alongside WNV within the Japanese encephalitis virus(JEV)serogroup of the Orthoflavivirus genus,the Flaviviridae family.USUV has spread from Africa to Europe since the late 20th century.It primarily causes central nervous system disorders in birds,with several large-scale mortality events recorded in Europe.USUV can also infect humans,it typically leads to neurological complications in rare cases(Roesch et al.,2019).展开更多
BACKGROUND Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I(rtCYE/rtCYEI)mutations in the hepatitis B virus(HBV)reverse-transcriptase(RT)region are associated with tenofovir disoproxil fumarate(TDF)resistance is ...BACKGROUND Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I(rtCYE/rtCYEI)mutations in the hepatitis B virus(HBV)reverse-transcriptase(RT)region are associated with tenofovir disoproxil fumarate(TDF)resistance is controversial.AIM To evaluate the presence of the rtCYE/rtCYEI mutations in a large cohort of Chinese patients with chronic HBV infection.METHODS A total of 28236 patients who underwent drug resistance testing at the Fifth Medical Center of Chinese PLA General Hospital from 2007 to 2019 were enrolled.All patients received nucleoside/nucleotide analogues(NAs)therapy,and serum samples were collected for sequence analysis of the HBV RT domain with mutation analysis.RESULTS The detection rates of a single mutation of rtS106C,rtH126Y,rtD134E,and rtL269I were 8.21%,3.20%,2.55%and 61.49%in 23718 genotype C patients,and 1.31%,1.76%,0.21%,and 92.33%in 4266 genotype B patients,respectively.The combined mutations of rtCYE/rtCYEI were only detected in 12 genotype C patients,accounting for 0.042%of all patients.These 12 patients had received NA treatments except TDF before testing.Among them,6 patients had coexisting rtCYE/rtCYEI and lamivudine-resistance mutations,and 2 patients had coexisting rtCYE/rtCYEI and adefovir-resistance mutations.Compared with the wild-type(WT)strain,the replication capacity of rtCYE/rtCYEI mutants from representative patients decreased by 41.1%-71.8%,and TDF susceptibility reduced by less than 2-fold,but rtCYEI+rtA181V/N236T mutants exhibited a 6.2-/9.9-fold decrease in TDF susceptibility.Molecular modeling showed that rtCYE/rtCYEI mutants had a slight decrease in binding energy to TDF compared to the WT strain.In the clinic,emergence of the rtCYE/rtCYEI mutations was not specifically associated with TDF treatment.CONCLUSION HBV rtCYE/rtCYEI mutations have a limited effect on TDF susceptibility and are not sufficient to cause TDF resistance.展开更多
Dear Editor,Viruses of the genus Orthoebolavirus cause sporadic outbreaks of severe haemorrhagic fever,with case fatality rates ranging from 25%to 90%(Mahanty and Bray,2004).Six species of the virus(Orthoebolavirus za...Dear Editor,Viruses of the genus Orthoebolavirus cause sporadic outbreaks of severe haemorrhagic fever,with case fatality rates ranging from 25%to 90%(Mahanty and Bray,2004).Six species of the virus(Orthoebolavirus zairense,sudanense,bundibugyoense,taiense,restonense,and bombaliense)have so far been identified(Biedenkopf et al.,2023).Among these,Orthoebolavirus zairense,commonly known as Ebola virus(EBOV),stands out as the most virulent.Given its high contagiousness and lethality,EBOV must be manipulated under biosafety level 4(BSL-4)conditions,as stipulated by the the People's Republic of China's list of human pathogenic microorganisms(National Health Commission of the People’s Republic of China,2023).Prior to being removed from a BSL-4 laboratory,it is imperative that infectious EBOV undergoes complete inactivation.Here we systematically evaluate viral thermostability under BSL-4 containment conditions,demonstrating EBOV's marked thermotolerance.展开更多
Objective:To uncover the characteristics of tick-borne viruses in Guizhou Province.Methods:A total of 414 Rhipicephalus microplus were collected from 5 counties in Guizhou Province,China from August 2022 to October 20...Objective:To uncover the characteristics of tick-borne viruses in Guizhou Province.Methods:A total of 414 Rhipicephalus microplus were collected from 5 counties in Guizhou Province,China from August 2022 to October 2023.A group of 12 ticks from each study sites was sequenced by next generation sequencing.Results:8 contigs of Wuhan mivirus(Chuviridae,Mivirus)with the length of 2094 bp to 11580 bp and 4 contigs of Lihan tick virus(Phenuiviridae,Uukuvirus)with the length of 1401 bp to 7080 bp were obtained,respectively.The prevalence rate of Wuhan mivirus and Lihan tick virus was 51.98%and 11.30%,respectively.The identities of gene sequences of both Wuhan mivirus and Lihan tick virus were 94%-100%compared with sequences in the National Center for Biotechnology Information.The phylogenetic analysis indicated that the Wuhan mivirus detected in this study was in the same branch with the Wuhan mivirus of Sichuan isolate TIGMIC-27(NCBI Accession:OP628598)and Zhejiang isolate TIGMIC-45(NCBI Accession:OP628613).In addition,the Lihan tick virus was in the same branch with the Sichuan Lihan tick virus isolate TIGMIC-46(NCBI Accession:ON812358).Conclusions:Both Wuhan mivirus and Lihan tick virus were prevalent in Rhipicephalus microplus in Guizhou Province.More studies are needed to understand the pathogenicity and public health threats of these tick-borne viruses.展开更多
Dengue virus(DENV)is a positive-sense single-stranded RNA virus belonging to the genus Flavivirus within the Flaviviridae family.Four serotypes,DENV 1-4,are distributed globally[1].Hanoi metropolitan city is an endemi...Dengue virus(DENV)is a positive-sense single-stranded RNA virus belonging to the genus Flavivirus within the Flaviviridae family.Four serotypes,DENV 1-4,are distributed globally[1].Hanoi metropolitan city is an endemic hotspot for DENV transmission in Vietnam[2,3].The largest outbreak occurred in 2017,with more than 36000 cases and 7 deaths reported,causing by all four serotypes with the predominance of DENV1,following by DENV2[4,5].During the following dengue season,we collected 390 blood and serum samples from 197 hospitalized patients in a national hospital in Hanoi city,Northern Vietnam to identify the circulating DENV serotypes responsible for the 2018-2019 outbreak.展开更多
The study of virus-host interactions has been significantly advanced using model organisms,with nematodes being a prominent example.Caenorhabditis elegans(C.elegans)nematodes have provided valuable insights into the m...The study of virus-host interactions has been significantly advanced using model organisms,with nematodes being a prominent example.Caenorhabditis elegans(C.elegans)nematodes have provided valuable insights into the mechanisms of viral infections,host defense strategies,and the development of antiviral therapies.With the discovery of natural viral pathogens of nematodes,Orsay virus,Le Blanc virus,Santeuil virus,and Mělník virus,the exploration of the virus-host interaction model based on nematodes has entered a new era.The virus-host interaction network consists of viruses,hosts,and the antagonistic effects of viruses on host immunity.The nematode virus-host interaction model is a concrete manifestation used to study the complex relationships among these three elements.Previous studies have indicated that during the entire process of nematode infection by viruses,antiviral RNA interference(RNAi)plays a crucial role.Additionally,the host’s innate immune responses,such as the antiviral-specific intracellular pathogen response(IPR)and certain signaling pathways homologous to those in humans,are particularly important in the natural immune and antiviral processes of nematodes.These processes are regulated by multiple genes in the host.The reverse genetics system for Orsay virus has been successfully developed to study viral gene function and virus-host interactions.Nematodes serve as simple host models for understanding RNA virus replication,related cellular components,and virus-host interaction mechanisms.These findings will likely contribute to the development of antiviral treatment strategies based on novel targets.展开更多
Dear Editor,In recent decades,vector-transmitted emerging and re-emerging diseases pose public health issues around the world,in which emerging tick-borne viruses(TBVs)have played a major role since they are widely di...Dear Editor,In recent decades,vector-transmitted emerging and re-emerging diseases pose public health issues around the world,in which emerging tick-borne viruses(TBVs)have played a major role since they are widely distributed.TBVs have a wide range of hosts,including humans,livestock and rodents,with some of them able to cause severe diseases in human and domestic animals,such as Jingmen tick virus(JMTV)(Qin et al.,2014),tick-borne encephalitis virus(TBEV)(Xing et al.,2017),and Alongshan virus(ALSV)(Wang et al.,2019).Of the merging TBVs,JMTV is a novel pathogen that was first identified in Rhipicephalus microplus collected from the Jingmen city of Hubei province,China in 2010(Qin et al.,2014).展开更多
The family Hepeviridae has seen an explosive expansion in its host range in recent years,yet the evolutionary trajectory of this zoonotic pathogen remains largely unknown.The emergence of rat hepatitis E virus(HEV)has...The family Hepeviridae has seen an explosive expansion in its host range in recent years,yet the evolutionary trajectory of this zoonotic pathogen remains largely unknown.The emergence of rat hepatitis E virus(HEV)has introduced a new public health threat due to its potential for zoonotic transmission.This study investigated2?464 wild small mammals spanning four animal orders,eight families,21 genera,and 37 species in Yunnan Province,China.Using broadly reactive reverse transcription-polymerase chain reaction(RT-PCR),we systematically screened the presence and prevalence of Orthohepevirus and identified 192 positive specimens from10 species,corresponding to an overall detection rate of7.79%.Next-generation sequencing enabled the recovery of 24 full-length genomic sequences from eight host species,including Bandicota bengalensis,Eothenomys eleusis,and Episoriculus caudatus,representing newly reported host species for Orthohepevirus strains.Phylogenetic and sequence analyses revealed extensive genetic diversity within orthohepeviruses infecting rodents and shrews.Notably,among the identified strains,20 were classified as Rocahepevirus ratti C1,two as C3,and one as Rocahepevirus eothenomi,while the remaining strain exhibited significant divergence,precluding classification.Evolutionary analyses highlighted close associations between orthohepeviruses and their respective host taxa,with distinct phylogenetic clustering patterns observed across different host orders.These findings emphasize the critical roles of co-speciation and cross-species transmission in shaping the evolutionary trajectories of the genera Paslahepevirus and Rocahepevirus.展开更多
AIM:To investigate the etiology of ocular pathogens and to establish the various pathogens present in human immunodeficiency virus(HIV)patients with cytomegalovirus retinitis(CMVR).METHODS:A total of 17 HIV-infected p...AIM:To investigate the etiology of ocular pathogens and to establish the various pathogens present in human immunodeficiency virus(HIV)patients with cytomegalovirus retinitis(CMVR).METHODS:A total of 17 HIV-infected patients with concomitant eye disorders were enrolled.Patients were divided into CMVR group(10 patients,18 eyes)and non-CMVR group(7 patients,9 eyes)based on clinical manifestations and the presence of cytomegalovirus(CMV)-DNA in ocular specimens.The viral load of CMV was assessed using polymerase chain reaction in aqueous humor,vitreous fluid,and peripheral blood samples of patients in the CMVR group.Additionally,peripheral blood CD4^(+)T cell counts were measured in both groups.RESULTS:In the CMVR group,the CMV-DNA load in the vitreous and aqueous humor samples was substantially higher than in the peripheral blood samples(P<0.01).CMVDNA load in the aqueous humor and vitreous samples of the two eyes in the CMVR group was determined to be statistically significant(10 patients,16 eyes,P=0.018,0.012).Peripheral blood CD4^(+)T cell counts in the CMVR group were adversely linked with the CMV-DNA load in both the aqueous humor and peripheral blood(P=0.005,0.048).Compared with the non-CMVR group,the peripheral blood CD4^(+)T cell count in the CMVR group decreased significantly(P=0.014).The peripheral blood CD4^(+)T cell count exceeded 300 cells/μL in 85.71%of non-CMVR patients,whereas it was below 100 cells/μL in 90.00%of the CMVR group.The intraocular specimens of the patients who underwent CMVR testing did not include any additional infections.CONCLUSION:In HIV-associated CMVR patients,there may exist alternative,yet unidentified,infection pathways for intraocular CMV in addition to the conventional route.The substantial difference in CMV-DNA load between the eyes of most CMVR patients suggests that CMV may originate from different sources in each eye.The proportion of peripheral blood CD4^(+)T cells in HIV patients is negatively correlated with the quantity of CMV viruses in their eyes.The peripheral blood count of<100 cells/μL indicates a considerable increase in the risk of concurrent CMVR.Multi-ocular pathogen presentations are uncommon in HIV individuals with CMVR.展开更多
In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B ...In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.展开更多
BACKGROUND Respiratory syncytial virus(RSV)is a leading cause of lower respiratory tract infections in neonates.While typically associated with bronchiolitis and pneumonia,RSV can rarely cause extrapulmonary complicat...BACKGROUND Respiratory syncytial virus(RSV)is a leading cause of lower respiratory tract infections in neonates.While typically associated with bronchiolitis and pneumonia,RSV can rarely cause extrapulmonary complications such as myocarditis,which may present with life-threatening symptoms if not promptly recognized.CASE SUMMARY We describe the case of a 26-day-old male neonate who presented with respiratory distress,poor feeding,and irritability.Initial evaluation revealed an RSV infection confirmed via nasopharyngeal swab.As the clinical course progressed,the infant developed cardiac arrhythmias,elevated cardiac enzymes,and echocardiographic findings consistent with myocarditis.Management included mechanical ventilation,corticosteroid therapy,L-carnitine,and vitamin D supplementation.The patient responded well to treatment and was successfully extubated and discharged in stable condition after nine days of hospitalization.CONCLUSION This case highlights the importance of early recognition and multidisciplinary management of RSV-associated myocarditis in neonates.展开更多
Mammals are critical reservoirs of human infectious diseases and the spillover of viruses is related to climate conditions.We conducted meta-transcriptomic sequencing of 226 mammals(bats,rodents,hedgehogs,and shrews)r...Mammals are critical reservoirs of human infectious diseases and the spillover of viruses is related to climate conditions.We conducted meta-transcriptomic sequencing of 226 mammals(bats,rodents,hedgehogs,and shrews)representing 20 species collected across eight cities in south China between 2018 and 2024.Samples included internal organs,oropharyngeal and anal swabs,and feces.We identified 63 vertebrate-associated viruses,including 34 novel viruses.Phylogenetic analysis revealed six viruses with potential infection risks to humans or domestic animals due to their close phylogenetic relationships with known pathogens.Cross-species transmission was observed in 14.3%(9/63)of viruses,shared by at least two host species,with bats,particularly Rhinolophus and Hipposideros,serving as key hubs for viral circulation and zoonotic spillover.Virome composition varied substantially among mammalian species and geographic regions(adonis test,R^(2)=0.50,P=0.001).Generalized linear models quantified the roles of host taxonomy,ecotypes,and meteorological factors in shaping viral diversity,demonstrating host taxonomy(at the order level)as a predominant role(25.70%deviance explained),followed by ecotypes(10.27%deviance explained).Phylogenetic analysis conducted using our betacoronavirus sequences,as well as betacoronavirus sequences derived from 2.0×10^(4) bats sampled in China between July 2013 and March 2024,revealed that no betacoronaviruses exhibited closer phylogenetic relationships to SARS-CoV-2 than the known strains(e.g.,RaTG13).These findings provide critical insights into virus evolution,transmission,and ecological determinants,which are essential for the prevention of emerging infectious diseases.展开更多
Immunomodulatory cancer therapy is witnessing the rise of viral immunotherapy.The oncolytic influenza A virus,although promising in preclinical investigations,remains to be implemented in clinical practice.Recent prog...Immunomodulatory cancer therapy is witnessing the rise of viral immunotherapy.The oncolytic influenza A virus,although promising in preclinical investigations,remains to be implemented in clinical practice.Recent progress in genetic engineering,coupled with experiential insights,offers opportunities to enhance the therapeutic efficacy of the influenza A virus.This review explores the use of the influenza virus,its attenuated forms,and associated vaccines in cancer immunotherapy,highlighting their respective advantages and challenges.We further elucidate methods for engineering influenza viruses and innovative approaches to augment them with cytokines or immune checkpoint inhibitors,aiming to maximize their clinical impact.Our goal is to provide insights essential for refining influenza A virus-based viral tumor immunotherapies.展开更多
BACKGROUND Hepatitis D virus-hepatitis B virus(HDV-HBV)co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma,but the immunopathogenic mechanism of its combination with a...BACKGROUND Hepatitis D virus-hepatitis B virus(HDV-HBV)co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma,but the immunopathogenic mechanism of its combination with autoimmune hepatitis(AIH)has not been clarified.This study reveals for the first time that HDV may induce AIH through abnormalities in immunoregulation in two specific cases.This is the first report of HDV-HBV co-infected patients who did not receive interferon therapy and achieved serological conversion and histological remission by combining antiviral(entecavir)with immunosuppression(prednisone+azathioprine)therapy,providing new evidence of the mechanism of this complex disease.CASE SUMMARY A 40-year-old female developed malaise and jaundice with an alanine aminotransferase/aspartate aminotransferase>20 upper limit of normal(ULN),total bilirubin:97.20μmol/L,immunoglobulin G(IgG)47.1 g/L(>3×ULN),HDV RNA 1.6×10^(7)copies/mL and liver biopsy showed G3S4.Tenofovir alafenamide combined with prednisone and azathioprine was administered,and three months later the Child-Turcotte-Pugh class C was reduced to class B and IgG decreased to 13.62 g/L.Another 58-year-old male complained of pain in the liver area,antinuclear antibody was 1:320,IgG 22.6 g/L(>1.3×ULN),and liver biopsy showed G2S3.Entecavir was administered in combination with prednisone and azathioprine,and after 3 months,liver function returned to normal,and IgG reduced to 14.22 g/L.CONCLUSION Patients with HDV-HBV co-infection combined with AIH can achieve clinical remission following combination therapy,and the study of immunomodulatory mechanisms should be emphasized.展开更多
Background:Vaccinia virus(VACV)and mpox virus(MPXV)belong to the orthopoxvirus genus and share high genetic similarity,making VACV widely used in the mpox pandemic.CAST/EiJ mice have been widely used for studying orth...Background:Vaccinia virus(VACV)and mpox virus(MPXV)belong to the orthopoxvirus genus and share high genetic similarity,making VACV widely used in the mpox pandemic.CAST/EiJ mice have been widely used for studying orthopoxvirus infection.However,the histopathological features of CAST/EiJ mice with mpox virus(MPXV)and vaccinia virus(VACV)infections have not been fully elucidated.Methods:Four group of CAST/EiJ mice were challenged with low-dose VACV(103 PFU,VACV-L),high-dose VACV(106 PFU,VACV-H),MPXV(106 PFU)or PBS via intraperitoneal route,and the disease signs and body weight were monitored daily.Subsequently,viral loads and titers in the blood and spleen of CAST/EiJ mice were analyzed via qPCR and TCID 50 assay.Finally,the spleen samples were analyzed for histopathological,immunohistochemical and RNA-seq.Results:Herein,we found that VACV-L and MPXV caused splenomegaly via the intraperitoneal route,whereas VACV-H caused rapid lethality with limited splenomegaly.Transcriptome analysis from spleen revealed significant differences in gene expression between VACV-L and VACV-H groups,but the differentially expressed genes induced by splenomegaly between VACV-L and MPXV groups were highly similar.Furthermore,pathway enrichment analysis demonstrated that the VACV-L,VACV-H,and MPXV groups were all associated with the calcium,MAPK,and PI3K-Akt signaling pathway.Compared to the lethal infection observed in VACV-H group,the splenomegaly in the VACV-L and MPXV groups was characterized by extramedullary hematopoiesis and increased macrophages infiltration in the red pulp.Transcriptome analysis of the spleen demonstrated that the Wnt,tumor necrosis factor(TNF),and transforming growth factorβ(TGF-β)signaling pathways may promote splenomegaly by modulating granulocyte infiltration and inflammatory responses.Compared to VACV-L group,the limited splenomegaly but lethality in VACV-H-infected mice might be associated with extensive splenic necrosis,diffuse congestion,and hemorrhage in the red pulp,as well as changes in the cGMP-PKG,Ras signaling,and Fc gamma Rmediated phagocytosis pathways.Conclusions:Our findings systematically compared the pathogenicity of VACV and MPXV in CAST/EiJ mice,incorporating splenic transcriptome analysis to provide insights into the potential molecular mechanism behind orthopoxvirus-induced splenomegaly in CAST/EiJ mice.展开更多
Dear Editor,Hepatitis B virus(HBV)is a small,enveloped DNA virus and a member of the Hepadnaviridae family(Zhao et al.,2020).It is a major human pathogen causing chronic liver disease,leading to significant morbidity ...Dear Editor,Hepatitis B virus(HBV)is a small,enveloped DNA virus and a member of the Hepadnaviridae family(Zhao et al.,2020).It is a major human pathogen causing chronic liver disease,leading to significant morbidity and mortality worldwide(Xia and Liang,2019).According to the World Health Organization(WHO),an estimated 296 million people live with chronic HBV infection,contributing to around 820,000 deaths annually due to complications such as liver cirrhosis and hepatocellular carcinoma(HCC)(Easterbrook et al.,2021).展开更多
Background:Whether chronic hepatitis B or C virus infection is a risk factor for autoimmune liver diseases(AILDs)remains unclear.This study aimed to investigate the causal relationship between the two disease entities...Background:Whether chronic hepatitis B or C virus infection is a risk factor for autoimmune liver diseases(AILDs)remains unclear.This study aimed to investigate the causal relationship between the two disease entities and underlying mechanisms.Methods:Bidirectional Mendelian randomization analysis was performed using genome-wide association study summary statistics for hepatitis B or C virus infection and AILDs in individuals of European ancestry.Statistically significant findings underwent meta-analysis for validation and single-cell RNA-seq were conducted to explore the potential mechanisms.Results:A causal relationship was observed between chronic hepatitis B virus(HBV)infection and an elevated risk of primary biliary cholangitis(PBC).Meta-analysis of all PBC-outcome findings confirmed the association(Odds ratio:1.32,95%confidence interval:1.23–1.42)without a reverse causal effect.Chronic HBV infection was also potentially associated with an increased risk of autoimmune hepatitis,but not with primary sclerosing cholangitis.No causal relationship was found between hepatitis C virus infection and AILDs.Single-cell RNA-seq revealed HLA gene activated in liver and impaired innate immune suppressive function in chronic hepatitis B patients.Conclusion:This study demonstrates a one-way causal association between chronic HBV infection and certain AILDs(PBC and autoimmune hepatitis),but not chronic hepatitis C virus infection.Single-cell transcriptome analysis revealed immune dysfunction caused by chronic HBV infection persists and is difficult to resolve even after HBV clearance,potentially leading to autoimmune hepatic diseases.展开更多
Marburg virus disease(MVD)is a highly fatal illness,with a case fatality rate of up to 88%,though this rate can be significantly reduced with prompt and effective patient care.The disease was first identified in 1967 ...Marburg virus disease(MVD)is a highly fatal illness,with a case fatality rate of up to 88%,though this rate can be significantly reduced with prompt and effective patient care.The disease was first identified in 1967 during concurrent outbreaks in Marburg and Frankfurt,Germany,and in Belgrade,Serbia,linked to laboratory use of African green monkeys imported from Uganda.Subsequent outbreaks and isolated cases have been reported in various African countries,including Angola,the Democratic Republic of the Congo,Equatorial Guinea,Ghana,Guinea,Kenya,Rwanda,South Africa(in an individual with recent travel to Zimbabwe),Tanzania,and Uganda.Initial human MVD infections typically occur due to prolonged exposure to mines or caves inhabited by Rousettus aegyptiacus fruit bats,the natural hosts of the virus.展开更多
文摘Periodontitis is the inflammation of the supporting structures around the dentition.Several microbial agents,mostly bacteria,have been identified as causative factors for periodontal disease.On the other hand,oral cavity is a rich reservoir for viruses since it contains a wide variety of cell types that can be targeted by viruses.Traditionally,the focus of research about the oral flora has been on bacteria because the most widespread oral diseases,like periodontitis and dental caries,are outcomes of bacterial infection.However,recently and especially after the emergence of coronavirus disease 2019,there is a growing tendency toward including viruses also into the scope of oral microbiome investigations.The global high prevalence of periodontitis and viral infections may point out to a concomitant or synergistic effect between the two.Although the exact nature of the mechanism still is not clearly understood,this could be speculated through the manipulation of the immune system by viruses;hence facilitating the furthermore colonization of the oral tissues by bacteria.This review provides an extensive and detailed update on the role of the most common viruses including herpes family(herpes simplex,varicella-zoster,Epstein-Barr,cytomegalovirus),Human papillomaviruses,Human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2 in the initiation,progression and prognosis of periodontitis.
文摘BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.
基金funded by grants from the National Key Research and Development Program of China(2022YFD1801900)National Natural Science Foundation of China(32272976&32302848)+3 种基金Sichuan Provincial Department of Science and Technology international scientific and technological innovation cooperation(2022YFH0026)the earmarked fund for China Agricultural Research System(CARS-42-17)Program Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System(SCCXTD-2021-18)the Innovation and Demonstration of Industry and Education Integration in Feed Industrial Chain Transformation and Upgradation,Sichuan Province,China.
文摘Dear Editor,For the past few decades,mosquito-borne orthoflaviviruses,such as dengue virus,Zika virus,and West Nile virus(WNV),have posed significant threats to global public health.The Orthoflavivirus genus comprises more than 70 viruses,many of which are responsible for a wide range of diseases in humans and animals,including febrile illnesses,encephalitis,and hemorrhagic febrile illness.These viruses are associated with approximately 400 million infections and 100 million symptomatic cases worldwide each year(Van Leur et al.,2021).Among them,Usutu virus(USUV)is an emerging pathogen classified alongside WNV within the Japanese encephalitis virus(JEV)serogroup of the Orthoflavivirus genus,the Flaviviridae family.USUV has spread from Africa to Europe since the late 20th century.It primarily causes central nervous system disorders in birds,with several large-scale mortality events recorded in Europe.USUV can also infect humans,it typically leads to neurological complications in rare cases(Roesch et al.,2019).
基金Supported by The National Natural Science Foundation of China,No.82470632.
文摘BACKGROUND Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I(rtCYE/rtCYEI)mutations in the hepatitis B virus(HBV)reverse-transcriptase(RT)region are associated with tenofovir disoproxil fumarate(TDF)resistance is controversial.AIM To evaluate the presence of the rtCYE/rtCYEI mutations in a large cohort of Chinese patients with chronic HBV infection.METHODS A total of 28236 patients who underwent drug resistance testing at the Fifth Medical Center of Chinese PLA General Hospital from 2007 to 2019 were enrolled.All patients received nucleoside/nucleotide analogues(NAs)therapy,and serum samples were collected for sequence analysis of the HBV RT domain with mutation analysis.RESULTS The detection rates of a single mutation of rtS106C,rtH126Y,rtD134E,and rtL269I were 8.21%,3.20%,2.55%and 61.49%in 23718 genotype C patients,and 1.31%,1.76%,0.21%,and 92.33%in 4266 genotype B patients,respectively.The combined mutations of rtCYE/rtCYEI were only detected in 12 genotype C patients,accounting for 0.042%of all patients.These 12 patients had received NA treatments except TDF before testing.Among them,6 patients had coexisting rtCYE/rtCYEI and lamivudine-resistance mutations,and 2 patients had coexisting rtCYE/rtCYEI and adefovir-resistance mutations.Compared with the wild-type(WT)strain,the replication capacity of rtCYE/rtCYEI mutants from representative patients decreased by 41.1%-71.8%,and TDF susceptibility reduced by less than 2-fold,but rtCYEI+rtA181V/N236T mutants exhibited a 6.2-/9.9-fold decrease in TDF susceptibility.Molecular modeling showed that rtCYE/rtCYEI mutants had a slight decrease in binding energy to TDF compared to the WT strain.In the clinic,emergence of the rtCYE/rtCYEI mutations was not specifically associated with TDF treatment.CONCLUSION HBV rtCYE/rtCYEI mutations have a limited effect on TDF susceptibility and are not sufficient to cause TDF resistance.
基金supported by the Youth Innovation Promotion Association of CAS(2023350 to Xiaoxiao Gao).
文摘Dear Editor,Viruses of the genus Orthoebolavirus cause sporadic outbreaks of severe haemorrhagic fever,with case fatality rates ranging from 25%to 90%(Mahanty and Bray,2004).Six species of the virus(Orthoebolavirus zairense,sudanense,bundibugyoense,taiense,restonense,and bombaliense)have so far been identified(Biedenkopf et al.,2023).Among these,Orthoebolavirus zairense,commonly known as Ebola virus(EBOV),stands out as the most virulent.Given its high contagiousness and lethality,EBOV must be manipulated under biosafety level 4(BSL-4)conditions,as stipulated by the the People's Republic of China's list of human pathogenic microorganisms(National Health Commission of the People’s Republic of China,2023).Prior to being removed from a BSL-4 laboratory,it is imperative that infectious EBOV undergoes complete inactivation.Here we systematically evaluate viral thermostability under BSL-4 containment conditions,demonstrating EBOV's marked thermotolerance.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82160633 and 81760605)the GZPH-NSFC-2021-17,the Guizhou Provincial Basic Research Program(Natural Science MS[2025](No.497)+1 种基金the Foundation of State Key Laboratory of Pathogen and Biosecurity of China(Grant No.SKLPBS2442)the High-level and Innovative Talents of Guizhou Province(QKH-GCC[2022]033-1).
文摘Objective:To uncover the characteristics of tick-borne viruses in Guizhou Province.Methods:A total of 414 Rhipicephalus microplus were collected from 5 counties in Guizhou Province,China from August 2022 to October 2023.A group of 12 ticks from each study sites was sequenced by next generation sequencing.Results:8 contigs of Wuhan mivirus(Chuviridae,Mivirus)with the length of 2094 bp to 11580 bp and 4 contigs of Lihan tick virus(Phenuiviridae,Uukuvirus)with the length of 1401 bp to 7080 bp were obtained,respectively.The prevalence rate of Wuhan mivirus and Lihan tick virus was 51.98%and 11.30%,respectively.The identities of gene sequences of both Wuhan mivirus and Lihan tick virus were 94%-100%compared with sequences in the National Center for Biotechnology Information.The phylogenetic analysis indicated that the Wuhan mivirus detected in this study was in the same branch with the Wuhan mivirus of Sichuan isolate TIGMIC-27(NCBI Accession:OP628598)and Zhejiang isolate TIGMIC-45(NCBI Accession:OP628613).In addition,the Lihan tick virus was in the same branch with the Sichuan Lihan tick virus isolate TIGMIC-46(NCBI Accession:ON812358).Conclusions:Both Wuhan mivirus and Lihan tick virus were prevalent in Rhipicephalus microplus in Guizhou Province.More studies are needed to understand the pathogenicity and public health threats of these tick-borne viruses.
基金the“Metropolitan Mosquitoes Project”funded by the Swedish Research Council for Environment,Agricultural Sciences and Spatial Planning(Formas,grant number 2016-00364).
文摘Dengue virus(DENV)is a positive-sense single-stranded RNA virus belonging to the genus Flavivirus within the Flaviviridae family.Four serotypes,DENV 1-4,are distributed globally[1].Hanoi metropolitan city is an endemic hotspot for DENV transmission in Vietnam[2,3].The largest outbreak occurred in 2017,with more than 36000 cases and 7 deaths reported,causing by all four serotypes with the predominance of DENV1,following by DENV2[4,5].During the following dengue season,we collected 390 blood and serum samples from 197 hospitalized patients in a national hospital in Hanoi city,Northern Vietnam to identify the circulating DENV serotypes responsible for the 2018-2019 outbreak.
基金supported by National Undergraduate Training Programs for Innovation and Entrepreneurship of Ministry of Education,China.
文摘The study of virus-host interactions has been significantly advanced using model organisms,with nematodes being a prominent example.Caenorhabditis elegans(C.elegans)nematodes have provided valuable insights into the mechanisms of viral infections,host defense strategies,and the development of antiviral therapies.With the discovery of natural viral pathogens of nematodes,Orsay virus,Le Blanc virus,Santeuil virus,and Mělník virus,the exploration of the virus-host interaction model based on nematodes has entered a new era.The virus-host interaction network consists of viruses,hosts,and the antagonistic effects of viruses on host immunity.The nematode virus-host interaction model is a concrete manifestation used to study the complex relationships among these three elements.Previous studies have indicated that during the entire process of nematode infection by viruses,antiviral RNA interference(RNAi)plays a crucial role.Additionally,the host’s innate immune responses,such as the antiviral-specific intracellular pathogen response(IPR)and certain signaling pathways homologous to those in humans,are particularly important in the natural immune and antiviral processes of nematodes.These processes are regulated by multiple genes in the host.The reverse genetics system for Orsay virus has been successfully developed to study viral gene function and virus-host interactions.Nematodes serve as simple host models for understanding RNA virus replication,related cellular components,and virus-host interaction mechanisms.These findings will likely contribute to the development of antiviral treatment strategies based on novel targets.
基金supported by Wildlife Borne Infectious Diseases Monitoring Project of the State Forestry and Grassland Administration of China(2020076060)the National Key Research and Development Program of China to Changchun Tu(32130104).
文摘Dear Editor,In recent decades,vector-transmitted emerging and re-emerging diseases pose public health issues around the world,in which emerging tick-borne viruses(TBVs)have played a major role since they are widely distributed.TBVs have a wide range of hosts,including humans,livestock and rodents,with some of them able to cause severe diseases in human and domestic animals,such as Jingmen tick virus(JMTV)(Qin et al.,2014),tick-borne encephalitis virus(TBEV)(Xing et al.,2017),and Alongshan virus(ALSV)(Wang et al.,2019).Of the merging TBVs,JMTV is a novel pathogen that was first identified in Rhipicephalus microplus collected from the Jingmen city of Hubei province,China in 2010(Qin et al.,2014).
基金supported by the National Natural Science Foundation of China (U2002218,81874274)Yunnan Health Training Project of High Level Talents (L-2017027)+3 种基金Project of Cross-border Control and Quarantine Innovation Group of Zoonosis of Dali University (ZKPY2019302)to Y.Z.ZOpen Project of Yunnan Key Laboratory of Biodiversity Information (BIKF22-02)Youth Innovation Promotion Association of the Chinese Academy of SciencesYunnan Revitalization Talent Support Program Young Talent Project to X.L.Y。
文摘The family Hepeviridae has seen an explosive expansion in its host range in recent years,yet the evolutionary trajectory of this zoonotic pathogen remains largely unknown.The emergence of rat hepatitis E virus(HEV)has introduced a new public health threat due to its potential for zoonotic transmission.This study investigated2?464 wild small mammals spanning four animal orders,eight families,21 genera,and 37 species in Yunnan Province,China.Using broadly reactive reverse transcription-polymerase chain reaction(RT-PCR),we systematically screened the presence and prevalence of Orthohepevirus and identified 192 positive specimens from10 species,corresponding to an overall detection rate of7.79%.Next-generation sequencing enabled the recovery of 24 full-length genomic sequences from eight host species,including Bandicota bengalensis,Eothenomys eleusis,and Episoriculus caudatus,representing newly reported host species for Orthohepevirus strains.Phylogenetic and sequence analyses revealed extensive genetic diversity within orthohepeviruses infecting rodents and shrews.Notably,among the identified strains,20 were classified as Rocahepevirus ratti C1,two as C3,and one as Rocahepevirus eothenomi,while the remaining strain exhibited significant divergence,precluding classification.Evolutionary analyses highlighted close associations between orthohepeviruses and their respective host taxa,with distinct phylogenetic clustering patterns observed across different host orders.These findings emphasize the critical roles of co-speciation and cross-species transmission in shaping the evolutionary trajectories of the genera Paslahepevirus and Rocahepevirus.
基金Supported by the Self-funded Research Project of the Health and Family Planning Commission of Guangxi Zhuang Autonomous Region(No.Z2016325).
文摘AIM:To investigate the etiology of ocular pathogens and to establish the various pathogens present in human immunodeficiency virus(HIV)patients with cytomegalovirus retinitis(CMVR).METHODS:A total of 17 HIV-infected patients with concomitant eye disorders were enrolled.Patients were divided into CMVR group(10 patients,18 eyes)and non-CMVR group(7 patients,9 eyes)based on clinical manifestations and the presence of cytomegalovirus(CMV)-DNA in ocular specimens.The viral load of CMV was assessed using polymerase chain reaction in aqueous humor,vitreous fluid,and peripheral blood samples of patients in the CMVR group.Additionally,peripheral blood CD4^(+)T cell counts were measured in both groups.RESULTS:In the CMVR group,the CMV-DNA load in the vitreous and aqueous humor samples was substantially higher than in the peripheral blood samples(P<0.01).CMVDNA load in the aqueous humor and vitreous samples of the two eyes in the CMVR group was determined to be statistically significant(10 patients,16 eyes,P=0.018,0.012).Peripheral blood CD4^(+)T cell counts in the CMVR group were adversely linked with the CMV-DNA load in both the aqueous humor and peripheral blood(P=0.005,0.048).Compared with the non-CMVR group,the peripheral blood CD4^(+)T cell count in the CMVR group decreased significantly(P=0.014).The peripheral blood CD4^(+)T cell count exceeded 300 cells/μL in 85.71%of non-CMVR patients,whereas it was below 100 cells/μL in 90.00%of the CMVR group.The intraocular specimens of the patients who underwent CMVR testing did not include any additional infections.CONCLUSION:In HIV-associated CMVR patients,there may exist alternative,yet unidentified,infection pathways for intraocular CMV in addition to the conventional route.The substantial difference in CMV-DNA load between the eyes of most CMVR patients suggests that CMV may originate from different sources in each eye.The proportion of peripheral blood CD4^(+)T cells in HIV patients is negatively correlated with the quantity of CMV viruses in their eyes.The peripheral blood count of<100 cells/μL indicates a considerable increase in the risk of concurrent CMVR.Multi-ocular pathogen presentations are uncommon in HIV individuals with CMVR.
基金Supported by the Natural Science Foundation of China,No.81970529the Natural Science Foundation of Jilin Province,No.20230508074RC and No.YDZJ202401218ZYTS.
文摘In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.
文摘BACKGROUND Respiratory syncytial virus(RSV)is a leading cause of lower respiratory tract infections in neonates.While typically associated with bronchiolitis and pneumonia,RSV can rarely cause extrapulmonary complications such as myocarditis,which may present with life-threatening symptoms if not promptly recognized.CASE SUMMARY We describe the case of a 26-day-old male neonate who presented with respiratory distress,poor feeding,and irritability.Initial evaluation revealed an RSV infection confirmed via nasopharyngeal swab.As the clinical course progressed,the infant developed cardiac arrhythmias,elevated cardiac enzymes,and echocardiographic findings consistent with myocarditis.Management included mechanical ventilation,corticosteroid therapy,L-carnitine,and vitamin D supplementation.The patient responded well to treatment and was successfully extubated and discharged in stable condition after nine days of hospitalization.CONCLUSION This case highlights the importance of early recognition and multidisciplinary management of RSV-associated myocarditis in neonates.
基金supported by the 3-year Public Health Program of the Shanghai Municipal Health Commission[grant number GWVI-11.1-10(GC)]the National Key Research and Development Program of China[grant number 2022YFC2602900(GC)]the Shanghai Municipal Health Commission[grant number 2022JC033(GC)].
文摘Mammals are critical reservoirs of human infectious diseases and the spillover of viruses is related to climate conditions.We conducted meta-transcriptomic sequencing of 226 mammals(bats,rodents,hedgehogs,and shrews)representing 20 species collected across eight cities in south China between 2018 and 2024.Samples included internal organs,oropharyngeal and anal swabs,and feces.We identified 63 vertebrate-associated viruses,including 34 novel viruses.Phylogenetic analysis revealed six viruses with potential infection risks to humans or domestic animals due to their close phylogenetic relationships with known pathogens.Cross-species transmission was observed in 14.3%(9/63)of viruses,shared by at least two host species,with bats,particularly Rhinolophus and Hipposideros,serving as key hubs for viral circulation and zoonotic spillover.Virome composition varied substantially among mammalian species and geographic regions(adonis test,R^(2)=0.50,P=0.001).Generalized linear models quantified the roles of host taxonomy,ecotypes,and meteorological factors in shaping viral diversity,demonstrating host taxonomy(at the order level)as a predominant role(25.70%deviance explained),followed by ecotypes(10.27%deviance explained).Phylogenetic analysis conducted using our betacoronavirus sequences,as well as betacoronavirus sequences derived from 2.0×10^(4) bats sampled in China between July 2013 and March 2024,revealed that no betacoronaviruses exhibited closer phylogenetic relationships to SARS-CoV-2 than the known strains(e.g.,RaTG13).These findings provide critical insights into virus evolution,transmission,and ecological determinants,which are essential for the prevention of emerging infectious diseases.
基金supported by the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang(No.2022R01002)the National Natural Science Foundation of China(Nos.82272300 and 82102893)the Fundamental Research Funds for the Central Universities(No.226-2024-00062),China.
文摘Immunomodulatory cancer therapy is witnessing the rise of viral immunotherapy.The oncolytic influenza A virus,although promising in preclinical investigations,remains to be implemented in clinical practice.Recent progress in genetic engineering,coupled with experiential insights,offers opportunities to enhance the therapeutic efficacy of the influenza A virus.This review explores the use of the influenza virus,its attenuated forms,and associated vaccines in cancer immunotherapy,highlighting their respective advantages and challenges.We further elucidate methods for engineering influenza viruses and innovative approaches to augment them with cytokines or immune checkpoint inhibitors,aiming to maximize their clinical impact.Our goal is to provide insights essential for refining influenza A virus-based viral tumor immunotherapies.
基金Supported by Xinjiang“Tianshan Talents”Medical and Health High-Level Talent Training Program-Young and Middle-Aged Backbone Medical Talents.
文摘BACKGROUND Hepatitis D virus-hepatitis B virus(HDV-HBV)co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma,but the immunopathogenic mechanism of its combination with autoimmune hepatitis(AIH)has not been clarified.This study reveals for the first time that HDV may induce AIH through abnormalities in immunoregulation in two specific cases.This is the first report of HDV-HBV co-infected patients who did not receive interferon therapy and achieved serological conversion and histological remission by combining antiviral(entecavir)with immunosuppression(prednisone+azathioprine)therapy,providing new evidence of the mechanism of this complex disease.CASE SUMMARY A 40-year-old female developed malaise and jaundice with an alanine aminotransferase/aspartate aminotransferase>20 upper limit of normal(ULN),total bilirubin:97.20μmol/L,immunoglobulin G(IgG)47.1 g/L(>3×ULN),HDV RNA 1.6×10^(7)copies/mL and liver biopsy showed G3S4.Tenofovir alafenamide combined with prednisone and azathioprine was administered,and three months later the Child-Turcotte-Pugh class C was reduced to class B and IgG decreased to 13.62 g/L.Another 58-year-old male complained of pain in the liver area,antinuclear antibody was 1:320,IgG 22.6 g/L(>1.3×ULN),and liver biopsy showed G2S3.Entecavir was administered in combination with prednisone and azathioprine,and after 3 months,liver function returned to normal,and IgG reduced to 14.22 g/L.CONCLUSION Patients with HDV-HBV co-infection combined with AIH can achieve clinical remission following combination therapy,and the study of immunomodulatory mechanisms should be emphasized.
基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,Grant/Award Number:2023-I2M-2-001National Key Research and Development Project of China,Grant/Award Number:2022YFC2304100 and 2023YFC2309000+1 种基金National Natural Science Foundation of China,Grant/Award Number:82241068 and 82222041Beijing Natural Science Foundation,Grant/Award Number:Z220018。
文摘Background:Vaccinia virus(VACV)and mpox virus(MPXV)belong to the orthopoxvirus genus and share high genetic similarity,making VACV widely used in the mpox pandemic.CAST/EiJ mice have been widely used for studying orthopoxvirus infection.However,the histopathological features of CAST/EiJ mice with mpox virus(MPXV)and vaccinia virus(VACV)infections have not been fully elucidated.Methods:Four group of CAST/EiJ mice were challenged with low-dose VACV(103 PFU,VACV-L),high-dose VACV(106 PFU,VACV-H),MPXV(106 PFU)or PBS via intraperitoneal route,and the disease signs and body weight were monitored daily.Subsequently,viral loads and titers in the blood and spleen of CAST/EiJ mice were analyzed via qPCR and TCID 50 assay.Finally,the spleen samples were analyzed for histopathological,immunohistochemical and RNA-seq.Results:Herein,we found that VACV-L and MPXV caused splenomegaly via the intraperitoneal route,whereas VACV-H caused rapid lethality with limited splenomegaly.Transcriptome analysis from spleen revealed significant differences in gene expression between VACV-L and VACV-H groups,but the differentially expressed genes induced by splenomegaly between VACV-L and MPXV groups were highly similar.Furthermore,pathway enrichment analysis demonstrated that the VACV-L,VACV-H,and MPXV groups were all associated with the calcium,MAPK,and PI3K-Akt signaling pathway.Compared to the lethal infection observed in VACV-H group,the splenomegaly in the VACV-L and MPXV groups was characterized by extramedullary hematopoiesis and increased macrophages infiltration in the red pulp.Transcriptome analysis of the spleen demonstrated that the Wnt,tumor necrosis factor(TNF),and transforming growth factorβ(TGF-β)signaling pathways may promote splenomegaly by modulating granulocyte infiltration and inflammatory responses.Compared to VACV-L group,the limited splenomegaly but lethality in VACV-H-infected mice might be associated with extensive splenic necrosis,diffuse congestion,and hemorrhage in the red pulp,as well as changes in the cGMP-PKG,Ras signaling,and Fc gamma Rmediated phagocytosis pathways.Conclusions:Our findings systematically compared the pathogenicity of VACV and MPXV in CAST/EiJ mice,incorporating splenic transcriptome analysis to provide insights into the potential molecular mechanism behind orthopoxvirus-induced splenomegaly in CAST/EiJ mice.
基金supported by the National Key Research and Development Program of China(No.2023YFC2308500)the Fundamental Research Funds for the Central Universities(project no.2042024kf0026),the Open Grant from the Pingyuan Laboratory(2023PY-OP-0101)+3 种基金the National Natural Science Foundation of China(project no.81971936,32100125 and 32300131)Hubei Province's Outstanding Medical Academic Leader Program,East Lake Hi-tech Development Zone Unveiling and Commanding Project(No.2023KJB219)Science and Technology Talent Service Enterprise Project(No.2024DJC064)Basic and Clinical Medical Research Joint Fund of Zhongnan Hospital,Wuhan University.
文摘Dear Editor,Hepatitis B virus(HBV)is a small,enveloped DNA virus and a member of the Hepadnaviridae family(Zhao et al.,2020).It is a major human pathogen causing chronic liver disease,leading to significant morbidity and mortality worldwide(Xia and Liang,2019).According to the World Health Organization(WHO),an estimated 296 million people live with chronic HBV infection,contributing to around 820,000 deaths annually due to complications such as liver cirrhosis and hepatocellular carcinoma(HCC)(Easterbrook et al.,2021).
基金supported by the National Natural Science Foundation of China(82270626)China Mega-Project for Infectious Diseases(2017ZX10203202,2013ZX10002005)the Project of Beijing Science and Technology Committee(Z191100007619037).
文摘Background:Whether chronic hepatitis B or C virus infection is a risk factor for autoimmune liver diseases(AILDs)remains unclear.This study aimed to investigate the causal relationship between the two disease entities and underlying mechanisms.Methods:Bidirectional Mendelian randomization analysis was performed using genome-wide association study summary statistics for hepatitis B or C virus infection and AILDs in individuals of European ancestry.Statistically significant findings underwent meta-analysis for validation and single-cell RNA-seq were conducted to explore the potential mechanisms.Results:A causal relationship was observed between chronic hepatitis B virus(HBV)infection and an elevated risk of primary biliary cholangitis(PBC).Meta-analysis of all PBC-outcome findings confirmed the association(Odds ratio:1.32,95%confidence interval:1.23–1.42)without a reverse causal effect.Chronic HBV infection was also potentially associated with an increased risk of autoimmune hepatitis,but not with primary sclerosing cholangitis.No causal relationship was found between hepatitis C virus infection and AILDs.Single-cell RNA-seq revealed HLA gene activated in liver and impaired innate immune suppressive function in chronic hepatitis B patients.Conclusion:This study demonstrates a one-way causal association between chronic HBV infection and certain AILDs(PBC and autoimmune hepatitis),but not chronic hepatitis C virus infection.Single-cell transcriptome analysis revealed immune dysfunction caused by chronic HBV infection persists and is difficult to resolve even after HBV clearance,potentially leading to autoimmune hepatic diseases.
文摘Marburg virus disease(MVD)is a highly fatal illness,with a case fatality rate of up to 88%,though this rate can be significantly reduced with prompt and effective patient care.The disease was first identified in 1967 during concurrent outbreaks in Marburg and Frankfurt,Germany,and in Belgrade,Serbia,linked to laboratory use of African green monkeys imported from Uganda.Subsequent outbreaks and isolated cases have been reported in various African countries,including Angola,the Democratic Republic of the Congo,Equatorial Guinea,Ghana,Guinea,Kenya,Rwanda,South Africa(in an individual with recent travel to Zimbabwe),Tanzania,and Uganda.Initial human MVD infections typically occur due to prolonged exposure to mines or caves inhabited by Rousettus aegyptiacus fruit bats,the natural hosts of the virus.
