The first event in viral infection is the attachment of a virus to specific receptors on the host cell surface. This will trigger conformational changes of the viral surface protein. For
Influenza A virus(IAV) has a wide host range,including wild birds,poultry,various mammals,and even humans(Xu et al.2024).Currently,two subtypes of canine influenza virus(CIV),H3N8 and H3N2,are primarily circulating in...Influenza A virus(IAV) has a wide host range,including wild birds,poultry,various mammals,and even humans(Xu et al.2024).Currently,two subtypes of canine influenza virus(CIV),H3N8 and H3N2,are primarily circulating in dogs.The H3N8 CIV was introduced from horses into dogs in 2004(Crawford et al.2005),while the H3N2 CIV originated from chickens in Asia in 2007(Song et al.2008).In China,H3N2 is the predominant CIV subtype,with a prevalence rate of up to 5.63% in the canine population,as reported by Chen et al.(2023).CIV infection typically manifests with symptoms such as coughing,sneezing,runny nose,and fever but is rarely fatal.However,co-infection with other pathogens(e.g.,Streptococcus,Mycoplasma or canine parainfluenza virus) can exacerbate symptoms and lead to lethal outcomes(Yondo et al.2023).展开更多
Oral immunization is an alternative or supplementary approach that can significantly improve dog vaccination coverage,especially for free-roaming dogs.Safe and effective oral rabies vaccines for dogs are still being s...Oral immunization is an alternative or supplementary approach that can significantly improve dog vaccination coverage,especially for free-roaming dogs.Safe and effective oral rabies vaccines for dogs are still being sought.In our previous studies,we generated a genetically modified rabies virus(RABV) ERA strain,rERAG_(333E),containing a mutation from arginine(Arg,R) to glutamic acid(Glu,E) at residue 333 of the G protein(G_(333E)).Our previous results demonstrated that rERAG_(333E) was safe for adult mice and dogs,and oral vaccination with rERAG_(333E) induced a strong and long-lasting protective immune response in dogs.Here,we further investigated the safety and immunogenicity of rERAG_(333E) in nontarget species,including suckling mice,rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.Suckling mice studies demonstrated that the G_(333E) mutation significantly reduced the virulence of the ERA strain.All of the suckling mice aged 10 days and above survived and showed no apparent signs of disease after intracerebral inoculation with rERAG_(333E).Animal studies demonstrated that rERAG_(333E) was safe in rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.None of those animals inoculated orally with 10 times the intended field dose of rERAG_(333E) showed abnormal clinical signs before and after the booster immunization with Rabvac 3,an inactivated rabies vaccine.Meanwhile,oral inoculation with rERAG_(333E) induced strong neutralizing antibody(NA) responses to RABV in rhesus monkeys,foxes,raccoon dogs,and piglets.These results demonstrated that rERAG_(333E) has the potential to serve as a safe oral rabies vaccine for dogs.展开更多
To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was struct...To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was structured around a project titled"Influenza Virus Analysis",comprising four progressive modules:database utilization and information retrieval,sequence alignment and phylogenetic analysis,functional and structural prediction,and omics data analysis.These modules were integrated into a coherent research workflow that connected fragmented knowledge and technical skills.During implementation,flipped classroom and group collaboration methods were employed,alongside the establishment of a diversified assessment system emphasizing process evaluation.Teaching practice indicates that the reform effectively enhances students professional application skills,learning experience,and scientific literacy,facilitating a shift from"tool operation"to"problem-solving"capabilities.This study provides a reference model for the reform of bioinformatics experimental teaching in local universities.展开更多
Decapod Iridescent Virus 1(DIV1)is a recently discovered virus recognized for its high infectivity in Macrobrachium rosenbergii.A thermal treatment was performed on DIV1-infected M.rosenbergii,and the therapeutic effi...Decapod Iridescent Virus 1(DIV1)is a recently discovered virus recognized for its high infectivity in Macrobrachium rosenbergii.A thermal treatment was performed on DIV1-infected M.rosenbergii,and the therapeutic efficacy was evaluated.In the DIV1 challenge experiment,the mortality rate in the challenged group was found to be 2.6 times greater than that in the control group,with the viral load in deceased individuals exceeding 5.41×10^(7)copies/μg-DNA.The thermal treatment(TT)was administered at 36℃for a duration of 16 d,followed by a temperature restoration(TR)period at 26℃for 3 d.On the first day at 36℃,an average viral concentration of 5.34×10 copies/μg-DNA was detected in the survived individuals.RNA-seq analysis showed a significant upregulation of genes related to the lysosome pathway,including sialin-like isoform x2(slc17a5),beta-galactosidase-1-like protein 2(glb1),putative glucosylceramidase 3(gba),sphingomyelin phosphodiesterase-like isoform x2(smpd1),betahexosaminidase subunit alpha-like(hexa_b)and legumain-like protein(lgmn),following a transient suppression period induced by thermal stress.Upon reaching 36℃,the activation of heat shock protein 70(hsp70)and heat shock protein 90(hsp90a)was observed.Concomitantly,genes that implicated in energy production critical for DIV1 replication,such as hexokinase(hk)and microsomal glutathione stransferase 3-like isoform x2(gst),were inhibited.These results collectively suggest that TT/TR treatments eliminated DIV1 in M.rosenbergii by activating the organism’s innate immune response and suppressing virus replication.This study provides a theoretical basis for utilizing thermal therapy in the management of viral infections in M.rosenbergii breeding programs,thereby facilitating the development of new strains resistant to DIV1.展开更多
Varicella,a highly contagious respiratory infection caused by the varicella-zoster virus(VZV),predominantly affects children and is characterized by symptoms such as low-grade fever and vesicular rash[1,2].In China,va...Varicella,a highly contagious respiratory infection caused by the varicella-zoster virus(VZV),predominantly affects children and is characterized by symptoms such as low-grade fever and vesicular rash[1,2].In China,varicella remains prevalent,with a steady increase in incidence,peaking at 70.14 cases per 100,000 individuals in 2019[3].Although the number of reported outbreaks and cases from 2020 to 2022 was lower than those from 2006 to 2012 and 2013 to 2019,varicella continues to pose a significant public health challenge[3].展开更多
Rabies is a zoonotic disease with an estimated global mortality of 59,000 people annually and a burden of more than 3.7 million disability-adjusted life years(DALYs)that is caused by a neurotropic lyssavirus[1].Dogs a...Rabies is a zoonotic disease with an estimated global mortality of 59,000 people annually and a burden of more than 3.7 million disability-adjusted life years(DALYs)that is caused by a neurotropic lyssavirus[1].Dogs are the primary source of human rabies,as more than 95%of human cases can be traced to dogs[2,3].China faces a substantial burden of rabies,having endured three major human rabies epidemics,which occurred in the 1950s,1981,and 2007[4].Implementation of various prevention and control measures has decreased the number of human rabies cases from 3,300 in 2007 to 167 in 2024.In China.展开更多
Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To over...Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To overcome these limitations,we used the NOG-EXL mice expressing human interleukin 3(IL-3)and granulocyte-macrophage colony-stimulating factor(GM-CSF)to enhance myeloid and B-cell lineage differentiation.Methods:Human CD34^(+)hematopoietic stem cells(HSC)were transplanted into NOG-EXL mice to produce humanized immune systems.After immune cell reconstitution was confirmed across 12 weeks,the mice were immunized twice with inactivated severe fever with thrombocytopenia syndrome virus(SFTSV)antigens.Peripheral blood mononuclear cells and splenocytes were analyzed using multicolor flow cytometry to assess human immune cell subsets.Antigen-specific immunoglobulin G(IgG)production was quantified using enzyme-linked immunosorbent assay(ELISA),and virus-specific B cells were isolated using antigen-labeled recombinant protein probes.Results:Twelve weeks after transplantation of HSCs into NOG-EXL mice,they exhibited robust engraftment of human leukocytes,including T,B,and dendritic cells,compared to NOG mice.Unlike NOG mice,humanized NOG-EXL mice exhibited an increase in human IgG levels,indicating the production of human antibody responses to antigens.Humanized NOG-EXL mice were immunized twice every 2 weeks with inactivated SFTSV,and antigen-specific human antibodies against the virus were detected in the mouse sera by ELISA.Sera from SFTSV-immunized humanized mice demonstrated neutralizing activity against SFTSV,confirming the induction of functional virus-specific neutralizing antibodies.Antigen-binding IgG-positive human B cells were isolated from mouse splenocytes using recombinant protein probes.Conclusion:This model provides a valuable platform for evaluating humoral immunity and isolating B cells using high-affinity human monoclonal antibodies without genetic engineering.展开更多
Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in...Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.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
Magnetic resonance imaging(MRI)is a powerful tool for diagnosing and monitoring brain diseases,but its low sensitivity can hinder early detection.To address this challenge,we utilized chemical exchange saturation tran...Magnetic resonance imaging(MRI)is a powerful tool for diagnosing and monitoring brain diseases,but its low sensitivity can hinder early detection.To address this challenge,we utilized chemical exchange saturation transfer(CEST)MRI,which greatly enhances sensitivity for detecting low-concentration compounds.In this study,we developed a CEST contrast agent based on a recombinant adeno-associated viruses(rAAVs)encoding the protamine-1(PRM1)MRI reporter gene.CEST MRI revealed that PRM1 contrast agent effectively highlighted caudate putamen region after injection of the rAAVs into the mouse brain,clearly distinguishing it from the surrounding tissue,with no observable damage.This method provides a sensitive,metal-free CEST contrast agent for in vivo brain cell detection,demonstrating potential for both diagnostic and therapeutic applications in brain diseases.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
Astrocytes are the most abundant glial cells in the central nervous system.They perform a diverse array of functions,with a critical role in structural integrity,synapse formation,and neurotransmission.These cells exh...Astrocytes are the most abundant glial cells in the central nervous system.They perform a diverse array of functions,with a critical role in structural integrity,synapse formation,and neurotransmission.These cells exhibit substantial regional heterogeneity and display variable responses to different neurological diseases.Such diversity in astrocyte morphology and function is essential for understanding both normal brain function and the underlying mechanisms of neurological disorders.To investigate this heterogeneity,we developed a novel method for the selective and sparse labeling of astrocytes in various brain regions.This technique utilizes a dual adeno-associated virus system that allows for the expression of Cre recombinase and enhanced green fluorescent protein under the control of the glial fibrillary acidic protein(GfaABC1D)promoter.The system was tested in C57BL/6J mice and successfully labeled astrocytes across multiple brain regions.The method enabled the detailed visualization of individual astrocytes-including their intricate peripheral processes-through three-dimensional reconstructions from confocal microscopy images.Furthermore,the labeling efficiency of this dual adeno-associated virus technology was validated by examining astrocyte function in a spared nerve injury model and through chemogenetic modulation.This innovative approach holds great promise for future research because it enables a more comprehensive understanding of astrocyte variation not only in spared nerve injury but also in a broad spectrum of neurological diseases.The ability to selectively label and study astrocytes in different brain regions provides a powerful tool for exploring the complexities of these essential cells and their roles in physiological and pathological conditions.展开更多
Mosquito-borne flaviviruses,such as Zika virus(ZIKV)and dengue virus(DENV),cause diverse severe clinical manifestations including fever,rash,hepatitis,arthralgia,and congenital anomalies.Here,we identified a host fact...Mosquito-borne flaviviruses,such as Zika virus(ZIKV)and dengue virus(DENV),cause diverse severe clinical manifestations including fever,rash,hepatitis,arthralgia,and congenital anomalies.Here,we identified a host factor,the adaptor protein complex 1 gamma 1 subunit(AP1G1),which plays an important role in both ZIKV and dengue virus 2(DENV2)infections.We explored the role of AP1G1 in ZIKV and DENV2 infections using CRISPR/Cas9 gene editing technology and RNA interference(RNAi)techniques.Knockout or silencing of AP1G1 decreases the replication of ZIKV and DENV2 in multiple human cell lines.Intriguingly,depletion of AP1G1 results in a significant reduction in ZIKV at an early stage,but decreases DENV2 replication levels during the late stage,suggesting that AP1G1 plays distinct roles in the infection by ZIKV and DENV2.Furthermore,we determined that AP1G1 mediates ZIKV-endosomal membrane fusion through inhibitor experiments and fluorescence labeling assays.Mechanistically,we found that AP1G1 exerts its pro-viral effect through binding to the ZIKV envelope glycoprotein(E protein).This interaction promotes the fusion of viral and endosomal membranes,during which the ZIKV genomic RNAs are released from the endosome into the cytoplasm,a process that facilitates viral replication.However,for DENV2 infection,AP1G1 primarily affects its viral RNA replication stage,rather than the fusion of virus-endosomal membrane.Taken together,our work demonstrates that AP1G1 plays a pro-viral role in both ZIKV and DENV2 infections via distinct mechanisms,highlighting its potential as a therapeutic target for antiviral strategies.展开更多
Coronaviruses(CoVs)are a large family of human and animal pathogens that cause significant health and economic burdens worldwide.Thapsigargin(Tg)is a plant-derived sesquiterpene lactone with potent antiviral effects;h...Coronaviruses(CoVs)are a large family of human and animal pathogens that cause significant health and economic burdens worldwide.Thapsigargin(Tg)is a plant-derived sesquiterpene lactone with potent antiviral effects;however,the underlying mechanism remains unclear.Here,we show that Tg exhibited strong antiviral activity against the neurotropic swine CoV porcine hemagglutinating encephalomyelitis virus(PHEV)both in vivo and in vitro.Tg also exhibited inhibitory activity against other three swine coronaviruses in cell lines.Specifically,Tg treatment significantly inhibited the replication and transcription of genomic RNA in the viral life cycle but did not directly inactivate PHEV.Transcriptome analysis and glycolysis/mitochondrial stress testing confirmed that Tg alters intracellular metabolic flux,and suppresses glycolysis and oxidative phosphorylation(OXPHOS).Furthermore,metabolic reprogramming is associated with the antiviral effect of Tg and is required for productive PHEV infection.Overall,our findings highlight that Tg plays a crucial role in combating viral infections by targeting host energy metabolism shared by pathogenic microorganisms,suggesting that targeting key nodes of host metabolic processes may be a strategy for designing antiviral drugs against coronaviruses.展开更多
Southern rice black-streaked dwarf disease is a new rice disease that severely affects rice production in South China.To understand transmission capacity of the vector Sogatella furcifera to Southern rice black-streak...Southern rice black-streaked dwarf disease is a new rice disease that severely affects rice production in South China.To understand transmission capacity of the vector Sogatella furcifera to Southern rice black-streaked dwarf virus（SRBSDV） among different host plant species,potential host plants of SRBSDV collected from the diseased rice field and/or adjacent to the field in Hunan Province,China,were determined by RT-PCR,and the transmission rates of SRBSDV by S.furcifera among different host plant species were investigated.The results showed that host plants of SRBSDV in the rice fields were five of family Gramineae（Oryza sativa,Echinochloa crusgalli,Zea mays,Paspalum distichum,Alopecurus aequali） and two of family Cyperaceae（Juncellus serotinus and Cyperus difformis）.S.furcifera could not transmit SRBSDV between gramineous plants and cyperaceous plants,and could not transmit SRBSDV between the gramineous plants,J.serotinus and C.difformis as well.However,SRBSDV could be transmitted by S.furcifera within gramineous plants.S.furcifera could transmit SRBSDV between interspecies among three species plants（O.sativa,E.crusgalli and Z.mays）,and between P.distichum and A.aequali.At 15,20,25,30,and 35°C,both macropterous and brachypterous adult of S.furcifera could transmit SRBSDV from the plants（e.g.,E.crusgalli,Z.mays and O.sativa） infected with SRBSDV to rice seedlings.The transmission rates were first increased and then decreased with the increase of temperature.Macropterous adults transmitted SRBSDV from the viruliferous E.crusgalli,Z.may and rice plants to the healthy rice seedlings,and the infected rates of rice seedlings were 26.2,18.8 and 23.7% at 15°C,56.6,64.6 and 53.6% at 25°C,and was 11.2,10.2 and 7.3% at 35°C,respectively.Transmission capacity of brachypterous adults was significantly higher than that of macropterous adults at 15,20 and 25°C（P0.05）,while transmission capacity of brachypterous adults was relatively lower compared with that of macropterous ones at 35°C.These results offer evidence on the transmission of SRBSDV via the vector S.furcifer among different host plants,which can be helpful to control Southern rice black-streaked dwarf disease by the appropriate cultural measures in South China.展开更多
To investigate whether transcription of hepatitis B virus （HBV） gene occurs in human sperm, total RNA was extracted from sperm of patients with chronic HBV infection （test-I）, from donor sperm transfected with a p...To investigate whether transcription of hepatitis B virus （HBV） gene occurs in human sperm, total RNA was extracted from sperm of patients with chronic HBV infection （test-I）, from donor sperm transfected with a plasmid containing the full-length HBV genome （test-2）, and from nontransfected donor sperm （control）, used as the template for reverse transcription-polymerase chain reaction （RT-PCR）. Positive bands for HBV DNA were observed in the test groups but not in the control. Next, to identify the role of host genes in regulating viral gene transcription in sperm, total RNA was extracted from 2-cell embryos derived from hamster oocytes fertilized in vitro by HBV-transfected （test） or nontransfected （control） human sperm and successively subjected to SMART-PCR, suppression subtractive hybridization, T/A cloning, bacterial amplification, microarray hybridization, sequencing and the Basic Local Alignment Search Tool （BLAST） search to isolate differentially expressed genes. Twenty-nine sequences showing significant identity to five human gene families were identified, with chorionic somatomammotropin hormone 2 （CSH2）, eukaryotic translation initiation factor 4 gamma 2 （EIF4G2）, pterin-4 alpha-carbinolamine dehydratase 2 （PCBD2）, pregnancy-specific beta-l-glycoprotein 4 （PSG4） and titin （TTN） selected to represent target genes. Using real-time quantitative RT-PCR （qRT-PCR）, when CSH2 and PCBD2 （or EIF4G2, PSG4 and TTN） were silenced by RNA interference, transcriptional levels of HBV s and x genes significantly decreased （or increased） （P 〈 0.05）. Silencing of a control gene in sperm did not significantly change transcription of HBV s and x genes （P 〉 0.05）. This study provides the first experimental evidence that transcription of HBV genes occurs in human sperm and is regulated by host genes.展开更多
The current therapeutic regimen to combat chronic hepatitis C is not optimal due to substantial side effects and the failure of a significant proportion of patients to achieve a sustained virological response. Recentl...The current therapeutic regimen to combat chronic hepatitis C is not optimal due to substantial side effects and the failure of a significant proportion of patients to achieve a sustained virological response. Recently developed direct-acting antivirals targeting hepatitis C virus (HCV) enzymes reportedly increase the virologic response to therapy but may lead to a selection of drug-resistant variants. Besides direct-acting antivirals, another promising class of HCV drugs in development include host targeting agents that are responsible for interfering with the host factors crucial for the viral life cycle. A family of host proteins known as DEAD-box RNA helicases, characterized by nine conserved motifs, is known to play an important role in RNA metabolism. Several members of this family such as DDX3, DDX5 and DDX6 have been shown to play a role in HCV replication and this review will summarize our current knowledge on their interaction with HCV. As chronic hepatitis C is one of the leading causes of hepatocellular carcinoma, the involvement of DEAD-box RNA helicases in the development of HCC will also be highlighted. Continuing research on the interaction of host DEAD-box proteins with HCV and the contribution to viral replication and pathogenesis could be the panacea for the development of novel therapeutics against HCV.展开更多
Dengue virus(DENV) belongs to the genus Flavivirus of the family Flaviviridae and it is primarily transmitted via Aedes aegypti and Aedes albopictus mosquitoes. The life cycle of DENV includes attachment, endocytosis,...Dengue virus(DENV) belongs to the genus Flavivirus of the family Flaviviridae and it is primarily transmitted via Aedes aegypti and Aedes albopictus mosquitoes. The life cycle of DENV includes attachment, endocytosis, protein translation, RNA synthesis, assembly, egress, and maturation.Recent researches have indicated that a variety of host factors, including cellular proteins and micro RNAs, positively or negatively regulate the DENV replication process. This review summarizes the latest findings(from 2014 to 2016) in the identification of the host factors involved in the DENV life cycle and Dengue infection.展开更多
文摘The first event in viral infection is the attachment of a virus to specific receptors on the host cell surface. This will trigger conformational changes of the viral surface protein. For
基金supported by the National Key Research and Development Program of China (2021YFD1800200)the National Natural Science Foundation of China (32170539)。
文摘Influenza A virus(IAV) has a wide host range,including wild birds,poultry,various mammals,and even humans(Xu et al.2024).Currently,two subtypes of canine influenza virus(CIV),H3N8 and H3N2,are primarily circulating in dogs.The H3N8 CIV was introduced from horses into dogs in 2004(Crawford et al.2005),while the H3N2 CIV originated from chickens in Asia in 2007(Song et al.2008).In China,H3N2 is the predominant CIV subtype,with a prevalence rate of up to 5.63% in the canine population,as reported by Chen et al.(2023).CIV infection typically manifests with symptoms such as coughing,sneezing,runny nose,and fever but is rarely fatal.However,co-infection with other pathogens(e.g.,Streptococcus,Mycoplasma or canine parainfluenza virus) can exacerbate symptoms and lead to lethal outcomes(Yondo et al.2023).
基金supported by the Natural Science Foundation of Heilongjiang Province,China (YQ2022C040)。
文摘Oral immunization is an alternative or supplementary approach that can significantly improve dog vaccination coverage,especially for free-roaming dogs.Safe and effective oral rabies vaccines for dogs are still being sought.In our previous studies,we generated a genetically modified rabies virus(RABV) ERA strain,rERAG_(333E),containing a mutation from arginine(Arg,R) to glutamic acid(Glu,E) at residue 333 of the G protein(G_(333E)).Our previous results demonstrated that rERAG_(333E) was safe for adult mice and dogs,and oral vaccination with rERAG_(333E) induced a strong and long-lasting protective immune response in dogs.Here,we further investigated the safety and immunogenicity of rERAG_(333E) in nontarget species,including suckling mice,rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.Suckling mice studies demonstrated that the G_(333E) mutation significantly reduced the virulence of the ERA strain.All of the suckling mice aged 10 days and above survived and showed no apparent signs of disease after intracerebral inoculation with rERAG_(333E).Animal studies demonstrated that rERAG_(333E) was safe in rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.None of those animals inoculated orally with 10 times the intended field dose of rERAG_(333E) showed abnormal clinical signs before and after the booster immunization with Rabvac 3,an inactivated rabies vaccine.Meanwhile,oral inoculation with rERAG_(333E) induced strong neutralizing antibody(NA) responses to RABV in rhesus monkeys,foxes,raccoon dogs,and piglets.These results demonstrated that rERAG_(333E) has the potential to serve as a safe oral rabies vaccine for dogs.
基金Supported by Undergraduate Higher Education Teaching Quality and Reform Projects of Guangdong Province(Yuejiao Gao Han[2024]No.9,Yuejiao Gao Han[2024]No.30)Guangdong Basic and Applied Basic Research Foundation(2023A1515110973)+1 种基金Guangdong Provincial Young Innovative Talents Project of General Colleges and Universities(2023KQNCX089)Quality Engineering and Teaching Reform Projects of Zhaoqing University(zlgc202239,zlgc202207,zlgc2024005,zlgc2024038).
文摘To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was structured around a project titled"Influenza Virus Analysis",comprising four progressive modules:database utilization and information retrieval,sequence alignment and phylogenetic analysis,functional and structural prediction,and omics data analysis.These modules were integrated into a coherent research workflow that connected fragmented knowledge and technical skills.During implementation,flipped classroom and group collaboration methods were employed,alongside the establishment of a diversified assessment system emphasizing process evaluation.Teaching practice indicates that the reform effectively enhances students professional application skills,learning experience,and scientific literacy,facilitating a shift from"tool operation"to"problem-solving"capabilities.This study provides a reference model for the reform of bioinformatics experimental teaching in local universities.
基金Supported by the earmarked fund for CARS(No.CARS-48)the National Natural Science Foundation of China(No.32202964)。
文摘Decapod Iridescent Virus 1(DIV1)is a recently discovered virus recognized for its high infectivity in Macrobrachium rosenbergii.A thermal treatment was performed on DIV1-infected M.rosenbergii,and the therapeutic efficacy was evaluated.In the DIV1 challenge experiment,the mortality rate in the challenged group was found to be 2.6 times greater than that in the control group,with the viral load in deceased individuals exceeding 5.41×10^(7)copies/μg-DNA.The thermal treatment(TT)was administered at 36℃for a duration of 16 d,followed by a temperature restoration(TR)period at 26℃for 3 d.On the first day at 36℃,an average viral concentration of 5.34×10 copies/μg-DNA was detected in the survived individuals.RNA-seq analysis showed a significant upregulation of genes related to the lysosome pathway,including sialin-like isoform x2(slc17a5),beta-galactosidase-1-like protein 2(glb1),putative glucosylceramidase 3(gba),sphingomyelin phosphodiesterase-like isoform x2(smpd1),betahexosaminidase subunit alpha-like(hexa_b)and legumain-like protein(lgmn),following a transient suppression period induced by thermal stress.Upon reaching 36℃,the activation of heat shock protein 70(hsp70)and heat shock protein 90(hsp90a)was observed.Concomitantly,genes that implicated in energy production critical for DIV1 replication,such as hexokinase(hk)and microsomal glutathione stransferase 3-like isoform x2(gst),were inhibited.These results collectively suggest that TT/TR treatments eliminated DIV1 in M.rosenbergii by activating the organism’s innate immune response and suppressing virus replication.This study provides a theoretical basis for utilizing thermal therapy in the management of viral infections in M.rosenbergii breeding programs,thereby facilitating the development of new strains resistant to DIV1.
文摘Varicella,a highly contagious respiratory infection caused by the varicella-zoster virus(VZV),predominantly affects children and is characterized by symptoms such as low-grade fever and vesicular rash[1,2].In China,varicella remains prevalent,with a steady increase in incidence,peaking at 70.14 cases per 100,000 individuals in 2019[3].Although the number of reported outbreaks and cases from 2020 to 2022 was lower than those from 2006 to 2012 and 2013 to 2019,varicella continues to pose a significant public health challenge[3].
文摘Rabies is a zoonotic disease with an estimated global mortality of 59,000 people annually and a burden of more than 3.7 million disability-adjusted life years(DALYs)that is caused by a neurotropic lyssavirus[1].Dogs are the primary source of human rabies,as more than 95%of human cases can be traced to dogs[2,3].China faces a substantial burden of rabies,having endured three major human rabies epidemics,which occurred in the 1950s,1981,and 2007[4].Implementation of various prevention and control measures has decreased the number of human rabies cases from 3,300 in 2007 to 167 in 2024.In China.
基金The Korea Centers for Disease Control and Prevention,Grant/Award Number:2022-ER1701-00,2022-NI-041-02,2024-ER1702-00 and 2025-NI-014-00。
文摘Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To overcome these limitations,we used the NOG-EXL mice expressing human interleukin 3(IL-3)and granulocyte-macrophage colony-stimulating factor(GM-CSF)to enhance myeloid and B-cell lineage differentiation.Methods:Human CD34^(+)hematopoietic stem cells(HSC)were transplanted into NOG-EXL mice to produce humanized immune systems.After immune cell reconstitution was confirmed across 12 weeks,the mice were immunized twice with inactivated severe fever with thrombocytopenia syndrome virus(SFTSV)antigens.Peripheral blood mononuclear cells and splenocytes were analyzed using multicolor flow cytometry to assess human immune cell subsets.Antigen-specific immunoglobulin G(IgG)production was quantified using enzyme-linked immunosorbent assay(ELISA),and virus-specific B cells were isolated using antigen-labeled recombinant protein probes.Results:Twelve weeks after transplantation of HSCs into NOG-EXL mice,they exhibited robust engraftment of human leukocytes,including T,B,and dendritic cells,compared to NOG mice.Unlike NOG mice,humanized NOG-EXL mice exhibited an increase in human IgG levels,indicating the production of human antibody responses to antigens.Humanized NOG-EXL mice were immunized twice every 2 weeks with inactivated SFTSV,and antigen-specific human antibodies against the virus were detected in the mouse sera by ELISA.Sera from SFTSV-immunized humanized mice demonstrated neutralizing activity against SFTSV,confirming the induction of functional virus-specific neutralizing antibodies.Antigen-binding IgG-positive human B cells were isolated from mouse splenocytes using recombinant protein probes.Conclusion:This model provides a valuable platform for evaluating humoral immunity and isolating B cells using high-affinity human monoclonal antibodies without genetic engineering.
基金supported by the National Natural Science Foundation of China,No.82471327the Natural Science Foundation of ShandongProvince,No.ZR2024MH200(both to SL).
文摘Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.
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financially supported by the National Natural Science Foundation of China(82127802,22374157)Strategic Priority Research Program,CAS(XDB0540000,XDC0170000)CAS Youth Interdisciplinary Team(JCTD-2022-13).In addition,Xin Zhou acknowledges the support from the Tencent Foundation through the XPLORER PRIZE.
文摘Magnetic resonance imaging(MRI)is a powerful tool for diagnosing and monitoring brain diseases,but its low sensitivity can hinder early detection.To address this challenge,we utilized chemical exchange saturation transfer(CEST)MRI,which greatly enhances sensitivity for detecting low-concentration compounds.In this study,we developed a CEST contrast agent based on a recombinant adeno-associated viruses(rAAVs)encoding the protamine-1(PRM1)MRI reporter gene.CEST MRI revealed that PRM1 contrast agent effectively highlighted caudate putamen region after injection of the rAAVs into the mouse brain,clearly distinguishing it from the surrounding tissue,with no observable damage.This method provides a sensitive,metal-free CEST contrast agent for in vivo brain cell detection,demonstrating potential for both diagnostic and therapeutic applications in brain diseases.
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National Natural Science Foundation of China,No.32271148(to JW)the National Key Research and the Development Program of China,No.2023M740625(to ML)+1 种基金the Natural Science Foundation of Guangdong Province,Nos.2021B1515120050(to HW)and 2023A1515110782(to ML)and Key R&D Program of Ningxia Hui Autonomous Region,No.2024BEG02027(to JW).
文摘Astrocytes are the most abundant glial cells in the central nervous system.They perform a diverse array of functions,with a critical role in structural integrity,synapse formation,and neurotransmission.These cells exhibit substantial regional heterogeneity and display variable responses to different neurological diseases.Such diversity in astrocyte morphology and function is essential for understanding both normal brain function and the underlying mechanisms of neurological disorders.To investigate this heterogeneity,we developed a novel method for the selective and sparse labeling of astrocytes in various brain regions.This technique utilizes a dual adeno-associated virus system that allows for the expression of Cre recombinase and enhanced green fluorescent protein under the control of the glial fibrillary acidic protein(GfaABC1D)promoter.The system was tested in C57BL/6J mice and successfully labeled astrocytes across multiple brain regions.The method enabled the detailed visualization of individual astrocytes-including their intricate peripheral processes-through three-dimensional reconstructions from confocal microscopy images.Furthermore,the labeling efficiency of this dual adeno-associated virus technology was validated by examining astrocyte function in a spared nerve injury model and through chemogenetic modulation.This innovative approach holds great promise for future research because it enables a more comprehensive understanding of astrocyte variation not only in spared nerve injury but also in a broad spectrum of neurological diseases.The ability to selectively label and study astrocytes in different brain regions provides a powerful tool for exploring the complexities of these essential cells and their roles in physiological and pathological conditions.
基金supported by the National Natural Science Foundation of China(No.82471389,No.32470986,No.82271385)Natural Science Foundation of Guangdong Province(No.2024A1515010471).
文摘Mosquito-borne flaviviruses,such as Zika virus(ZIKV)and dengue virus(DENV),cause diverse severe clinical manifestations including fever,rash,hepatitis,arthralgia,and congenital anomalies.Here,we identified a host factor,the adaptor protein complex 1 gamma 1 subunit(AP1G1),which plays an important role in both ZIKV and dengue virus 2(DENV2)infections.We explored the role of AP1G1 in ZIKV and DENV2 infections using CRISPR/Cas9 gene editing technology and RNA interference(RNAi)techniques.Knockout or silencing of AP1G1 decreases the replication of ZIKV and DENV2 in multiple human cell lines.Intriguingly,depletion of AP1G1 results in a significant reduction in ZIKV at an early stage,but decreases DENV2 replication levels during the late stage,suggesting that AP1G1 plays distinct roles in the infection by ZIKV and DENV2.Furthermore,we determined that AP1G1 mediates ZIKV-endosomal membrane fusion through inhibitor experiments and fluorescence labeling assays.Mechanistically,we found that AP1G1 exerts its pro-viral effect through binding to the ZIKV envelope glycoprotein(E protein).This interaction promotes the fusion of viral and endosomal membranes,during which the ZIKV genomic RNAs are released from the endosome into the cytoplasm,a process that facilitates viral replication.However,for DENV2 infection,AP1G1 primarily affects its viral RNA replication stage,rather than the fusion of virus-endosomal membrane.Taken together,our work demonstrates that AP1G1 plays a pro-viral role in both ZIKV and DENV2 infections via distinct mechanisms,highlighting its potential as a therapeutic target for antiviral strategies.
基金supported by the National Key Research and Development Program of China under Grant 2022YFD1801400 to Zi Lithe National Natural Science Foundation of China under Grants 32302851 to Junchao Shi,32272956 to Zi Li,32172828 to Wenqi Hethe Natural Science Foundation Project of Jilin Province under Grant 20240101014JC to Zi Li.
文摘Coronaviruses(CoVs)are a large family of human and animal pathogens that cause significant health and economic burdens worldwide.Thapsigargin(Tg)is a plant-derived sesquiterpene lactone with potent antiviral effects;however,the underlying mechanism remains unclear.Here,we show that Tg exhibited strong antiviral activity against the neurotropic swine CoV porcine hemagglutinating encephalomyelitis virus(PHEV)both in vivo and in vitro.Tg also exhibited inhibitory activity against other three swine coronaviruses in cell lines.Specifically,Tg treatment significantly inhibited the replication and transcription of genomic RNA in the viral life cycle but did not directly inactivate PHEV.Transcriptome analysis and glycolysis/mitochondrial stress testing confirmed that Tg alters intracellular metabolic flux,and suppresses glycolysis and oxidative phosphorylation(OXPHOS).Furthermore,metabolic reprogramming is associated with the antiviral effect of Tg and is required for productive PHEV infection.Overall,our findings highlight that Tg plays a crucial role in combating viral infections by targeting host energy metabolism shared by pathogenic microorganisms,suggesting that targeting key nodes of host metabolic processes may be a strategy for designing antiviral drugs against coronaviruses.
基金funded by the Key Programme of Hunan Provincial Science & Technology Bureau(2011NK2009)
文摘Southern rice black-streaked dwarf disease is a new rice disease that severely affects rice production in South China.To understand transmission capacity of the vector Sogatella furcifera to Southern rice black-streaked dwarf virus（SRBSDV） among different host plant species,potential host plants of SRBSDV collected from the diseased rice field and/or adjacent to the field in Hunan Province,China,were determined by RT-PCR,and the transmission rates of SRBSDV by S.furcifera among different host plant species were investigated.The results showed that host plants of SRBSDV in the rice fields were five of family Gramineae（Oryza sativa,Echinochloa crusgalli,Zea mays,Paspalum distichum,Alopecurus aequali） and two of family Cyperaceae（Juncellus serotinus and Cyperus difformis）.S.furcifera could not transmit SRBSDV between gramineous plants and cyperaceous plants,and could not transmit SRBSDV between the gramineous plants,J.serotinus and C.difformis as well.However,SRBSDV could be transmitted by S.furcifera within gramineous plants.S.furcifera could transmit SRBSDV between interspecies among three species plants（O.sativa,E.crusgalli and Z.mays）,and between P.distichum and A.aequali.At 15,20,25,30,and 35°C,both macropterous and brachypterous adult of S.furcifera could transmit SRBSDV from the plants（e.g.,E.crusgalli,Z.mays and O.sativa） infected with SRBSDV to rice seedlings.The transmission rates were first increased and then decreased with the increase of temperature.Macropterous adults transmitted SRBSDV from the viruliferous E.crusgalli,Z.may and rice plants to the healthy rice seedlings,and the infected rates of rice seedlings were 26.2,18.8 and 23.7% at 15°C,56.6,64.6 and 53.6% at 25°C,and was 11.2,10.2 and 7.3% at 35°C,respectively.Transmission capacity of brachypterous adults was significantly higher than that of macropterous adults at 15,20 and 25°C（P0.05）,while transmission capacity of brachypterous adults was relatively lower compared with that of macropterous ones at 35°C.These results offer evidence on the transmission of SRBSDV via the vector S.furcifer among different host plants,which can be helpful to control Southern rice black-streaked dwarf disease by the appropriate cultural measures in South China.
基金This work was supported by the National Natural Science Foundation of China （No. 30972526） and by the Applied Basic Research Programs of Sichuan Province （No. 20141Y0110）. The authors thank Prof. Stanley Lin for his assistance in revising the final draft of the manuscript and editing for English grammar and syntax.
文摘To investigate whether transcription of hepatitis B virus （HBV） gene occurs in human sperm, total RNA was extracted from sperm of patients with chronic HBV infection （test-I）, from donor sperm transfected with a plasmid containing the full-length HBV genome （test-2）, and from nontransfected donor sperm （control）, used as the template for reverse transcription-polymerase chain reaction （RT-PCR）. Positive bands for HBV DNA were observed in the test groups but not in the control. Next, to identify the role of host genes in regulating viral gene transcription in sperm, total RNA was extracted from 2-cell embryos derived from hamster oocytes fertilized in vitro by HBV-transfected （test） or nontransfected （control） human sperm and successively subjected to SMART-PCR, suppression subtractive hybridization, T/A cloning, bacterial amplification, microarray hybridization, sequencing and the Basic Local Alignment Search Tool （BLAST） search to isolate differentially expressed genes. Twenty-nine sequences showing significant identity to five human gene families were identified, with chorionic somatomammotropin hormone 2 （CSH2）, eukaryotic translation initiation factor 4 gamma 2 （EIF4G2）, pterin-4 alpha-carbinolamine dehydratase 2 （PCBD2）, pregnancy-specific beta-l-glycoprotein 4 （PSG4） and titin （TTN） selected to represent target genes. Using real-time quantitative RT-PCR （qRT-PCR）, when CSH2 and PCBD2 （or EIF4G2, PSG4 and TTN） were silenced by RNA interference, transcriptional levels of HBV s and x genes significantly decreased （or increased） （P 〈 0.05）. Silencing of a control gene in sperm did not significantly change transcription of HBV s and x genes （P 〉 0.05）. This study provides the first experimental evidence that transcription of HBV genes occurs in human sperm and is regulated by host genes.
基金Supported by Grants from the Ministry of Education of Singapore,Academic Research Fund Tier 1 Grant R-182-000-170-112
文摘The current therapeutic regimen to combat chronic hepatitis C is not optimal due to substantial side effects and the failure of a significant proportion of patients to achieve a sustained virological response. Recently developed direct-acting antivirals targeting hepatitis C virus (HCV) enzymes reportedly increase the virologic response to therapy but may lead to a selection of drug-resistant variants. Besides direct-acting antivirals, another promising class of HCV drugs in development include host targeting agents that are responsible for interfering with the host factors crucial for the viral life cycle. A family of host proteins known as DEAD-box RNA helicases, characterized by nine conserved motifs, is known to play an important role in RNA metabolism. Several members of this family such as DDX3, DDX5 and DDX6 have been shown to play a role in HCV replication and this review will summarize our current knowledge on their interaction with HCV. As chronic hepatitis C is one of the leading causes of hepatocellular carcinoma, the involvement of DEAD-box RNA helicases in the development of HCC will also be highlighted. Continuing research on the interaction of host DEAD-box proteins with HCV and the contribution to viral replication and pathogenesis could be the panacea for the development of novel therapeutics against HCV.
基金supported by the National Natural Science Foundation of China (81371794)Guangdong Natural Science Foundation (2014A030311007)
文摘Dengue virus(DENV) belongs to the genus Flavivirus of the family Flaviviridae and it is primarily transmitted via Aedes aegypti and Aedes albopictus mosquitoes. The life cycle of DENV includes attachment, endocytosis, protein translation, RNA synthesis, assembly, egress, and maturation.Recent researches have indicated that a variety of host factors, including cellular proteins and micro RNAs, positively or negatively regulate the DENV replication process. This review summarizes the latest findings(from 2014 to 2016) in the identification of the host factors involved in the DENV life cycle and Dengue infection.
