Diel investigations of water environments are one means to holistically understand the dynamics and functional roles of phytoplankton,bacteria and viruses in these ecosystems.They have the potential to substantially i...Diel investigations of water environments are one means to holistically understand the dynamics and functional roles of phytoplankton,bacteria and viruses in these ecosystems.They have the potential to substantially impact carbon(C),nitrogen(N)and phosphorus(P)biogeochemistry through their respective roles.This study characterizes the phytoplankton,bacteria and virus communities and the elemental composition of various C,N and P nutrients flow over three diel cycles in tropical urban lake.Our results show that ratios of C:N:P fluctuated strongly from the lack of dissolved organic phosphorus(DOP)and PO_(4).Specifically,green algae peaked during day time and exudate dissolved organic matter(DOM)that strongly modulate dissolved organic carbon(DOC):DOP ratio to diel DOP limitation.Multiple linear regression and Stella modelling emphasize the roles of viruses together with Synechococcus as important nutrient recyclers of NH_(4)and PO_(4)in nutrients-limited waters.Respective normalised surface PO_(4)and combined surface and bottom NH_(4)concentration selected both viruses and Synechococcus as important drivers.Process model of N and P biogeochemical cycles can achieve 69%and 57%similar to observed concentration of NH_(4)and PO_(4),respectively.A short latent period of 9 hr was calculated,in addition to the calibrated high infectivity of viruses to Synechococcus.Taken together,the rapid turn-over between Synechococcus and viruses has biogeochemical significance,where the rapid recycling of essential nutrients allows for shortcuts in the N and P cycle,supporting a wide range of microbes.展开更多
A complex system is inherently high-dimensional.Recent studies indicate that,even without complete knowledge of its evolutionary dynamics,the future behavior of such a system can be predicted using time-series data(da...A complex system is inherently high-dimensional.Recent studies indicate that,even without complete knowledge of its evolutionary dynamics,the future behavior of such a system can be predicted using time-series data(data-driven prediction).This suggests that the essential dynamics of a complex system can be captured through a low-dimensional representation.Virus evolution and climate change are two examples of complex,time-varying systems.In this article,we show that mutations in the spike protein provide valuable data for predicting SARS-CoV-2 variants,forecasting the possible emergence of the new macro-lineage Q in the near future.Our analysis also demonstrates that carbon dioxide concentration is a reliable indicator for predicting the evolution of the climate system,extending global surface air temperature(GSAT)forecasts through 2500.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
Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not complet...Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.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
Viruses are significant pathogens causing severe plant infections and crop losses globally.The resistance mechanisms of rice to viral diseases,particularly Southern rice black-streaked dwarf virus(SRBSDV),remain poorl...Viruses are significant pathogens causing severe plant infections and crop losses globally.The resistance mechanisms of rice to viral diseases,particularly Southern rice black-streaked dwarf virus(SRBSDV),remain poorly understood.In this study,we assessed SRBSDV susceptibility in 20 Xian/indica(XI)and 20 Geng/japonica(GJ)rice varieties.XI-1B accessions in the Xian subgroup displayed higher resistance than GJ accessions.Comparative transcriptome analysis revealed changes in processes like oxidoreductase activity,jasmonic acid(JA)metabolism,and stress response.JA sensitivity assays further linked antiviral defense to the JA pathway.These findings highlight a JA-mediated resistance mechanism in rice and offer insights for breeding SRBSDV-resistant varieties.展开更多
Introduction: Arbovirus diseases such as dengue and chikungunya threaten public health worldwide. Early and rapid diagnosis and surveillance of dengue virus (DENV) and chikungunya virus (CHIKV) infections are essentia...Introduction: Arbovirus diseases such as dengue and chikungunya threaten public health worldwide. Early and rapid diagnosis and surveillance of dengue virus (DENV) and chikungunya virus (CHIKV) infections are essential to the control of these diseases. In this study, we evaluate the diagnostic performance of our new in-house multiplex RT-qPCR method for detecting DENV serotypes and CHIKV in an external laboratory. Methodology: The evaluation study was conducted on 200 clinical samples of suspected patients for arbovirus disease infection, collected in Centre de Recherche Biomoléculaire Pietro Annigoni (CERBA), Ouagadougou, Burkina Faso. Our new multiplex RT-qPCR was compared to the commercial kit, the Zika, Dengue, and Chikungunya (ZDC) Real-Time PCR Assays kit (Bio-Rad, California, USA). Results and Conclusions: Among 200 samples, 21.5% (43/200) were DENV-positive by multiplex RT-qPCR, and 21.5% (43/200) were also DENV-positive by reference real-time RT-PCR. 157 (78.5%) samples tested negative for DENV by both tests (new mRT-qPCR and reference test). The sensitivity and specificity of mRT-qPCR were 100%. The DENV serotypes detected were DENV-1 60.5% (26/43) and DENV-3 39.5% (17/43). CHIKV was not detected in this study. Our new mRT-qPCR is sensitive, cost-effective, simple, and can be used in developing country laboratories.展开更多
Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with t...Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.展开更多
Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has ...Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has been proved that traditional Chinese medicine(TCM)has displayed definite therapeutic effects on viral hemorrhagic fever,indicating its potential to treat SFTS.In this study,SFTS-relative key targets were predicted via gene ontology(GO)analysis and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Molecular docking was then used to select stable binders.Molecules matched TCMs were identified,and a new prescription,Qingqi Guxue decoction(QQGX),was formulated to clear heat and nourish blood,with a resulting drug composition network.We explored the optimal drug proportion for QQGX.Through an in-depth study of molecular mechanisms,we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2(CCNA2)and cyclin-dependent kinase 2(CDK2),thereby inhibiting SFTSV replication.Finally,we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV.In summary,our study prepared a TCM decoction using the method of network pharmacology.This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.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
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
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
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
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
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
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: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
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
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
文摘Diel investigations of water environments are one means to holistically understand the dynamics and functional roles of phytoplankton,bacteria and viruses in these ecosystems.They have the potential to substantially impact carbon(C),nitrogen(N)and phosphorus(P)biogeochemistry through their respective roles.This study characterizes the phytoplankton,bacteria and virus communities and the elemental composition of various C,N and P nutrients flow over three diel cycles in tropical urban lake.Our results show that ratios of C:N:P fluctuated strongly from the lack of dissolved organic phosphorus(DOP)and PO_(4).Specifically,green algae peaked during day time and exudate dissolved organic matter(DOM)that strongly modulate dissolved organic carbon(DOC):DOP ratio to diel DOP limitation.Multiple linear regression and Stella modelling emphasize the roles of viruses together with Synechococcus as important nutrient recyclers of NH_(4)and PO_(4)in nutrients-limited waters.Respective normalised surface PO_(4)and combined surface and bottom NH_(4)concentration selected both viruses and Synechococcus as important drivers.Process model of N and P biogeochemical cycles can achieve 69%and 57%similar to observed concentration of NH_(4)and PO_(4),respectively.A short latent period of 9 hr was calculated,in addition to the calibrated high infectivity of viruses to Synechococcus.Taken together,the rapid turn-over between Synechococcus and viruses has biogeochemical significance,where the rapid recycling of essential nutrients allows for shortcuts in the N and P cycle,supporting a wide range of microbes.
基金Natural science foundation of Inner Mongolia(2024LHMS06018)The basic scientific research funding for directly affiliated universities in the Inner Mongolia(JY20250094)。
文摘A complex system is inherently high-dimensional.Recent studies indicate that,even without complete knowledge of its evolutionary dynamics,the future behavior of such a system can be predicted using time-series data(data-driven prediction).This suggests that the essential dynamics of a complex system can be captured through a low-dimensional representation.Virus evolution and climate change are two examples of complex,time-varying systems.In this article,we show that mutations in the spike protein provide valuable data for predicting SARS-CoV-2 variants,forecasting the possible emergence of the new macro-lineage Q in the near future.Our analysis also demonstrates that carbon dioxide concentration is a reliable indicator for predicting the evolution of the climate system,extending global surface air temperature(GSAT)forecasts through 2500.
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 UniversitàCattolica(D1 intramural funds to RP)Italian Ministry of University and Research(PRIN 2022ZYLB7B,P2022YW7BP funds to CG).
文摘Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.
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.
基金funded by the National Key Research and Development Plan of China(2023YFD1400300)National Natural Science Foundation of China(U23A6006,32270149,32272555)+1 种基金Zhejiang Provincial Natural Science Foundation(LZ22C140001)the Ningbo Major Research and Development Plan Project(2023Z124).
文摘Viruses are significant pathogens causing severe plant infections and crop losses globally.The resistance mechanisms of rice to viral diseases,particularly Southern rice black-streaked dwarf virus(SRBSDV),remain poorly understood.In this study,we assessed SRBSDV susceptibility in 20 Xian/indica(XI)and 20 Geng/japonica(GJ)rice varieties.XI-1B accessions in the Xian subgroup displayed higher resistance than GJ accessions.Comparative transcriptome analysis revealed changes in processes like oxidoreductase activity,jasmonic acid(JA)metabolism,and stress response.JA sensitivity assays further linked antiviral defense to the JA pathway.These findings highlight a JA-mediated resistance mechanism in rice and offer insights for breeding SRBSDV-resistant varieties.
文摘Introduction: Arbovirus diseases such as dengue and chikungunya threaten public health worldwide. Early and rapid diagnosis and surveillance of dengue virus (DENV) and chikungunya virus (CHIKV) infections are essential to the control of these diseases. In this study, we evaluate the diagnostic performance of our new in-house multiplex RT-qPCR method for detecting DENV serotypes and CHIKV in an external laboratory. Methodology: The evaluation study was conducted on 200 clinical samples of suspected patients for arbovirus disease infection, collected in Centre de Recherche Biomoléculaire Pietro Annigoni (CERBA), Ouagadougou, Burkina Faso. Our new multiplex RT-qPCR was compared to the commercial kit, the Zika, Dengue, and Chikungunya (ZDC) Real-Time PCR Assays kit (Bio-Rad, California, USA). Results and Conclusions: Among 200 samples, 21.5% (43/200) were DENV-positive by multiplex RT-qPCR, and 21.5% (43/200) were also DENV-positive by reference real-time RT-PCR. 157 (78.5%) samples tested negative for DENV by both tests (new mRT-qPCR and reference test). The sensitivity and specificity of mRT-qPCR were 100%. The DENV serotypes detected were DENV-1 60.5% (26/43) and DENV-3 39.5% (17/43). CHIKV was not detected in this study. Our new mRT-qPCR is sensitive, cost-effective, simple, and can be used in developing country laboratories.
文摘Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.
基金supported by the National Natural Science Foundation of China(32170144 and 32470146).
文摘Severe fever with thrombocytopenia syndrome(SFTS)is a novel emerging acute infectious disease caused by severe fever with thrombocytopenia syndrome virus(SFTSV),characterized by high fever and thrombocytopenia.It has been proved that traditional Chinese medicine(TCM)has displayed definite therapeutic effects on viral hemorrhagic fever,indicating its potential to treat SFTS.In this study,SFTS-relative key targets were predicted via gene ontology(GO)analysis and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Molecular docking was then used to select stable binders.Molecules matched TCMs were identified,and a new prescription,Qingqi Guxue decoction(QQGX),was formulated to clear heat and nourish blood,with a resulting drug composition network.We explored the optimal drug proportion for QQGX.Through an in-depth study of molecular mechanisms,we found that QQGX induces S phase arrest by promoting the degradation of cyclin A2(CCNA2)and cyclin-dependent kinase 2(CDK2),thereby inhibiting SFTSV replication.Finally,we verified the effectiveness and safety of QQGX based on the mouse liver bile duct organoid model infected with SFTSV.In summary,our study prepared a TCM decoction using the method of network pharmacology.This decoction has a significant inhibitory effect on the replication of SFTSV and provides a new treatment strategy for hemorrhagic fever with TCM.
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 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.
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.
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 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 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.
