A switch from avian-typeα-2,3 to human-typeα-2,6 receptors is an essential element for the initiation of a pandemic from an avian influenza virus.Some H9N2 viruses exhibit a preference for binding to human-typeα-2,...A switch from avian-typeα-2,3 to human-typeα-2,6 receptors is an essential element for the initiation of a pandemic from an avian influenza virus.Some H9N2 viruses exhibit a preference for binding to human-typeα-2,6 receptors.This identifies their potential threat to public health.However,our understanding of the molecular basis for the switch of receptor preference is still limited.In this study,we employed the random forest algorithm to identify the potentially key amino acid sites within hemagglutinin(HA),which are associated with the receptor binding ability of H9N2 avian influenza virus(AIV).Subsequently,these sites were further verified by receptor binding assays.A total of 12 substitutions in the HA protein(N158D,N158S,A160 N,A160D,A160T,T163I,T163V,V190T,V190A,D193 N,D193G,and N231D)were predicted to prefer binding toα-2,6 receptors.Except for the V190T substitution,the other substitutions were demonstrated to display an affinity for preferential binding toα-2,6 receptors by receptor binding assays.Especially,the A160T substitution caused a significant upregulation of immune-response genes and an increased mortality rate in mice.Our findings provide novel insights into understanding the genetic basis of receptor preference of the H9N2 AIV.展开更多
Dear Editor,Historically,dipeptidyl peptidase 4(DPP4),found in alveolar regions,has been recognized as the primary receptor for several merbecoviruses like MERS-CoV(Meyerholz et al.,2016).However,angiotensin-convertin...Dear Editor,Historically,dipeptidyl peptidase 4(DPP4),found in alveolar regions,has been recognized as the primary receptor for several merbecoviruses like MERS-CoV(Meyerholz et al.,2016).However,angiotensin-converting enzyme 2(ACE2),highly expressed in the motile cilia of human airway epithelial cells(Sungnak et al.,2020),has been identified as the functional receptor for sarbecoviruses(e.g.,SARS-CoV-2,SARS-CoV)and setracoviruses(e.g.,HCoV-NL63).Recent studies have shown that some bat-circulating MERS-related coronaviruses(MERSr-CoVs),such as MOW15-22,PnNL2018B and HKU5,can use ACE2 to enter cells(Ma et al.,2025;Park et al.,2025).Even more worrying is that one novel bat-infecting merbecovirus HKU5-CoV lineage 2(BtHKU5-CoV-2)has been reported to use human ACE2 as a cell entry receptor(Chen et al.,2025).These ACE2-utilizing merbecoviruses expand the diversity,geographic distribution,and transmission potential of coronaviruses,posing a significant threat of spillover to humans.If an ACE2-utilizing MERSr-CoV acquire the high lethality of MERS-CoV and the high transmissibility of SARS-CoV-2 using ACE2 as a receptor,it could trigger a global pandemic with catastrophic consequences for humanity.Therefore,it is essential to evaluate serological cross-reactivity in sera from SARS-CoV-2-infected individuals against ACE2-using MERSr-CoVs,and urgent to develop preventive vaccines and pan-coronavirus antivirals confront the potential threat(Jiang and Wu,2025).展开更多
Some HIV-infected individuals receiving ART develop low-level viremia(LLV),with a plasma viral load of 50-1000 copies/mL.Persistent low-level viremia is associated with subsequent virologic failure.The peripheral bloo...Some HIV-infected individuals receiving ART develop low-level viremia(LLV),with a plasma viral load of 50-1000 copies/mL.Persistent low-level viremia is associated with subsequent virologic failure.The peripheral blood CD4^(+)T cell pool is a source of LLV.However,the intrinsic characteristics of CD4^(+)T cells in LLV which may contribute to low-level viremia are largely unknown.We analyzed the transcriptome profiling of peripheral blood CD4^(+)T cells from healthy controls(HC)and HIV-infected patients receiving ART with either virologic sup-pression(VS)or LLV.To identify pathways potentially responding to increasing viral loads from HC to VS and to LLV,KEGG pathways of differentially expressed genes(DEGs)were acquired by comparing VS with HC(VS-HC group)and LLV with VS(LLV-VS group),and overlapped pathways were analyzed.Characterization of DEGs in key overlapping pathways showed that CD4^(+)T cells in LLV expressed higher levels of Th1 signature transcription factors(TBX21),toll-like receptors(TLR-4,-6,-7 and-8),anti-HIV entry chemokines(CCL3 and CCL4),and anti-IL-1βfactors(ILRN and IL1R2)compared to VS.Our results also indicated activation of the NF-κB and TNF signaling pathways that could promote HIV-1 transcription.Finally,we evaluated the effects of 4 and 17 tran-scription factors that were upregulated in the VS-HC and LLV-VS groups,respectively,on HIV-1 promoter activity.Functional studies revealed that CXXC5 significantly increased,while SOX5 markedly suppressed HIV-1 tran-scription.In summary,we found that CD4^(+)T cells in LLV displayed a distinct mRNA profiling compared to that in VS,which promoted HIV-1 replication and r+eactivation of viral latency and may eventually contribute to virologic failure in patients with persistent LLV.CXXC5 and SOX5 may serve as targets for the development of latency-reversing agents.展开更多
Influenza A virus(IAV)genome comprises eight negative-sense RNA segments,of which the replication is well orchestrated and the delicate balance of multiple segments are dynamically regulated throughout IAV life cycle....Influenza A virus(IAV)genome comprises eight negative-sense RNA segments,of which the replication is well orchestrated and the delicate balance of multiple segments are dynamically regulated throughout IAV life cycle.However,previous studies seldom discuss these balances except for functional hemagglutinin-neuraminidase balance that is pivotal for both virus entry and release.Therefore,we attempt to revisit IAV life cycle by highlighting the critical role of“genome balance”.Moreover,we raise a“balance regression”model of IAV evolution that the virus evolves to rebalance its genome after reassortment or interspecies transmission,and direct a“balance compensation”strategy to rectify the“genome imbalance”as a result of artificial modifications during creation of recombinant IAVs.This review not only improves our understanding of IAV life cycle,but also facilitates both basic and applied research of IAV in future.展开更多
Ticks are considered the second most common pathogen vectors transmitting a broad range of vital human and veterinary viruses.From 2017 to 2018,640 ticks were collected in eight different provinces in central and west...Ticks are considered the second most common pathogen vectors transmitting a broad range of vital human and veterinary viruses.From 2017 to 2018,640 ticks were collected in eight different provinces in central and western China.Six species were detected,including H.longicornis,De.everestianus,Rh.microplus,Rh.turanicus,Rh.sanguineous,and Hy.asiaticum.Sixty-four viral metagenomic libraries were constructed on the MiSeq Illumina platform,resulting in 13.44 G(5.88×10^(7))of 250-bp-end reads,in which 2,437,941 are viral reads.We found 27 nearly complete genome sequences,including 16 genome sequences encoding entire protein-coding regions(lack of 30 or 50 end non-coding regions)and complete viral genomes,distributed in the arboviral family(Chuviridae,Rhabdoviridae,Nairoviridae,Phenuiviridae,Flaviviridae,Iflaviridae)as well as Parvoviridae and Polyomaviridae that cause disease in mammals and even humans.In addition,13 virus sequences found in Chuviridae,Nairoviridae,Flaviviridae,Iflaviridae,Hepeviridae,Parvoviridae,and Polyomaviridae were identified as belonging to a new virus species in the identified viral genera.Besides,an epidemiological survey shows a high prevalence(9.38%and 15.63%)of two viruses(Ovine Copiparvovirus and Bovine parvovirus 2)in the tick cohort.展开更多
Myocardial injury is one of the most common comorbidity in SARS-CoV-2 infected patients,and has poor prognosis.However,the incidence of myocardial injury in patients with SARS-CoV-2 infection has not been sufficiently...Myocardial injury is one of the most common comorbidity in SARS-CoV-2 infected patients,and has poor prognosis.However,the incidence of myocardial injury in patients with SARS-CoV-2 infection has not been sufficiently investigated during the Omicron wave.We conducted a retrospective study of 2690 patients with confirmed SARS-CoV-2 Omicron infection from Tongji Hospital.The results indicated that the myocardial injury accounted for 30.8%of the total patients with SARS-CoV-2 infection and was associated with higher in-hospital mortality than those without injury before and after propensity score matching(PSM)[adjusted hazard ratio(HR),10.61;95%confidence interval(CI),7.76–14.51;P<0.001;adjusted HR,2.70;95%CI,1.86–3.93;P<0.001;respectively].Further,the levels of cytokines(IL-1β,IL-6,IL-10,and TNF-α)in patients with myocardial injury were higher than those without injury,and the higher levels of cytokines in the myocardial injury group were associated with increased mortality.Administration of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers(ACEI/ARB)could significantly reduce the mortality in patients with myocardial injury(adjusted HR,0.52;95%CI,0.38–0.71;P<0.001).Additionally,the level of angiotensin II increased in patients with SARS-CoV-2 infection was even higher in myocardial injury group compared to those without injury.Collectively,the study summarized the clinical characteristic and outcome of SARS-CoV-2 infected patients with myocardial injury during the Omicron wave in China,and validated the protective role of ACEI/ARB in improving the survival of those with myocardial injury.展开更多
Dear Editor,Severe acute respiratory syndrome coronavirus-2(SARS-Co V-2)is a novel coronavirus that causes the outbreak of coronavirus disease 2019(COVID-19)(Li et al.,2020a).Viral nucleic acid testing is the standard...Dear Editor,Severe acute respiratory syndrome coronavirus-2(SARS-Co V-2)is a novel coronavirus that causes the outbreak of coronavirus disease 2019(COVID-19)(Li et al.,2020a).Viral nucleic acid testing is the standard method for the laboratory diagnosis of COVID-19(Wu et al.,2020a;Zhu et al.,2020).Currently,a variety of qPCR-based detection kits are used for laboratory-based detection and confirmation of SARS-CoV-2 infection(Corman et al.,2020;Hussein et al.,2020;Ruhan et al.,2020;Veyer et al.,2020).Conventional qPCR involves virus inactivation,nucleic acid extraction,and qPCR amplification procedures.Therefore,the process is complicated,which usually takes longer than 2 h,and requires biosafety laboratories and professional staff.Thus,qPCR is not suitable for use in field or medical units.展开更多
Arthropod-borne chikungunya virus(CHIKV)infection can cause a debilitating arthritic disease in human.However,there are no specific antiviral drugs and effective licensed vaccines against CHIKV available for clinical ...Arthropod-borne chikungunya virus(CHIKV)infection can cause a debilitating arthritic disease in human.However,there are no specific antiviral drugs and effective licensed vaccines against CHIKV available for clinical use.Here,we developed an m RNA-lipid nanoparticle(m RNA-LNP)vaccine expressing CHIKV E2-E1 antigen,and compared its immunogenicity with soluble recombinant protein s E2-E1 antigen expressed in S2 cells.For comparison,we first showed that recombinant protein antigens mixed with aluminum adjuvant elicit strong antigenspecific humoral immune response and a moderate cellular immune response in C57BL/6 mice.Moreover,s E2-E1vaccine stimulated 12-23 folds more neutralizing antibodies than s E1 vaccine and s E2 vaccine.Significantly,when E2-E1 gene was delivered by an m RNA-LNP vaccine,not only the better magnitude of neutralizing antibody responses was induced,but also greater cellular immune responses were generated,especially for CD8+T cell responses.Moreover,E2-E1-LNP induced CD8~+T cells can perform cytotoxic effect in vivo.Considering its better immunogenicity and convenience of preparation,we suggest that more attention should be placed to develop CHIKV E2-E1-LNP m RNA vaccine.展开更多
The CREB-regulated transcriptional co-activators(CRTCs),including CRTC1,CRTC2 and CRTC3,enhance transcription of CREB-targeted genes.In addition to regulating host gene expression in response to cAMP,CRTCs also increa...The CREB-regulated transcriptional co-activators(CRTCs),including CRTC1,CRTC2 and CRTC3,enhance transcription of CREB-targeted genes.In addition to regulating host gene expression in response to cAMP,CRTCs also increase the infection of several viruses.While human immunodeficiency virus type 1(HIV-1)long terminal repeat(LTR)promoter harbors a cAMP response element and activation of the cAMP pathway promotes HIV-1 transcription,it remains unknown whether CRTCs have any effect on HIV-1 transcription and HIV-1 infection.Here,we reported that CRTC2 expression was induced by HIV-1 infection,but CRTC2 suppressed HIV-1 infection and diminished viral RNA expression.Mechanistic studies revealed that CRTC2 inhibited transcription from HIV-1 LTR and diminished RNA PolⅡoccupancy at the LTR independent of its association with CREB.Importantly,CRTC2 inhibits the activation of latent HIV-1.Together,these data suggest that in response to HIV-1 infection,cells increase the expression of CRTC2 which inhibits HIV-1 gene expression and may play a role in driving HIV-1 into latency.展开更多
Dear Editor,Acute gastroenteritis(AGE)is a leading infectious cause of morbidity worldwide,particularly among children in developing countries(Mortality and Causes of Death2016).With the introduction of rotavirus vacc...Dear Editor,Acute gastroenteritis(AGE)is a leading infectious cause of morbidity worldwide,particularly among children in developing countries(Mortality and Causes of Death2016).With the introduction of rotavirus vaccines,noroviruses have been identified as a leading cause of AGE outbreaks and sporadic disease worldwide(Hall et al.展开更多
Infectious diseases pose a serious threat to human health and affect social,economic,and cultural development.Many infectious diseases,such as severe acute respiratory syndrome(SARS,2013),Middle East respiratory syndr...Infectious diseases pose a serious threat to human health and affect social,economic,and cultural development.Many infectious diseases,such as severe acute respiratory syndrome(SARS,2013),Middle East respiratory syndrome(MERS,2012 and 2013),Zika virus infection(2007,2013 and 2015),and coronavirus disease 2019(COVID-19,2019),have occurred as regional or global epidemics(Reperant and Osterhaus 2017;Gao 2018)。展开更多
Enterovirus A71(EV-A71) is the major pathogen responsible for the severe hand, foot and mouth disease worldwide, for which few effective antiviral drugs are presently available. Interferon-a(IFN-a) has been used in an...Enterovirus A71(EV-A71) is the major pathogen responsible for the severe hand, foot and mouth disease worldwide, for which few effective antiviral drugs are presently available. Interferon-a(IFN-a) has been used in antiviral therapy for decades;it has been reported that EV-A71 antagonizes the antiviral activity of IFN-a based on viral 2 Apro-mediated reduction of the interferon-alpha receptor 1(IFNAR1);however, the mechanism remains unknown. Here, we showed a significant increase in IFNAR1 protein induced by IFN-a in RD cells, whereas EV-A71 infection caused obvious downregulation of the IFNAR1 protein and blockage of IFN-a signaling. Subsequently, we observed that EV-A71 2 Apro inhibited IFNAR1 translation by cleavage of the eukaryotic initiation factor 4 GI(eIF4GI), without affecting IFNAR1 m RNA levels induced by IFN-a. The inhibition of IFNAR1 translation also occurred in puromycin-induced apoptotic cells when caspase-3 cleaved e IF4 GI. Importantly, we verified that 2 Aprocould activate cellular caspase-3, which was subsequently involved in e IF4 GI cleavage mediated by 2 Apro. Furthermore, inhibition of caspase-3 activation resulted in the partial restoration of IFNAR1 in cells transfected with 2 A or infected with EV-A71, suggesting the pivotal role of both viral 2 Aproand caspase-3 activation in the disturbance of IFN-a signaling. Collectively, we elucidate a novel mechanism by which cellular caspase-3 contributes to viral 2 Apro-mediated down-regulation of IFNAR1 at the translation level during EV-A71 infection, indicating that caspase-3 inhibition could be a potential complementary strategy to improve clinical anti-EV-A71 therapy with IFN-a.展开更多
Dear Editor,The hepatitis A virus(HAV)is a common agent causing acute liver disease worldwide,with approximately 11,000deaths annually(WHO 2017).The virus is transmitted primarily by the fecal-oral route and it normal...Dear Editor,The hepatitis A virus(HAV)is a common agent causing acute liver disease worldwide,with approximately 11,000deaths annually(WHO 2017).The virus is transmitted primarily by the fecal-oral route and it normally infects people living in high-density and resource-poor展开更多
Intravenous drug users(IDUs) have been demonstrated to be highly vulnerable to HIV/AIDS.Nevertheless, the prevalence of Kaposi's sarcoma associated herpesvirus(KSHV), an important co-infected agent with HIV, among...Intravenous drug users(IDUs) have been demonstrated to be highly vulnerable to HIV/AIDS.Nevertheless, the prevalence of Kaposi's sarcoma associated herpesvirus(KSHV), an important co-infected agent with HIV, among this population remained obscure. We conducted a systematic review on the epidemiological features of KSHV among IDUs worldwide. Eligible studies were retrieved from 6 electronic databases(Pub Med, EMBASE, Web of Science, CBM, CNKI and Wanfang).We calculated the pooled prevalence and 95% confidence interval(CI) overall and among subgroups using either random-effects model or fixed-effects model depending on between-study heterogeneity. The potential publication bias was assessed by the Egger's test. A meta-regression analysis was performed to explore the sources of heterogeneity. Finally, twenty-two studies with a total sample of 7881 IDUs were included in the analysis. The pooled prevalence of KSHV was14.71%(95% CI 11.12%–19.46%) among IDUs. Specifically, KSHV prevalence was 10.86%(95% CI6.95%–16.96%) in HIV-negative IDUs, and 13.56%(95% CI 10.57%–17.38%) in HIV-positive IDUs.Moreover, prevalence among IDUs from the three continents involved in the current study was similar:16.10%(95%CI 7.73%–33.54%) in Asia; 14.22%(95%CI 8.96%–22.57%) in Europe and 14.06%(95%CI11.38%–17.37%) in America. Globally, IDUs are at higher risk of the KSHV infection when compared with the general population, regardless of geographical region or HIV-infection status.展开更多
This special issue of the journal is dedicated to the important topic of oncogenic viruses and cancer.It contains seven review articles covering all known oncogenic viruses except for human T-lymphotropic virus type1(...This special issue of the journal is dedicated to the important topic of oncogenic viruses and cancer.It contains seven review articles covering all known oncogenic viruses except for human T-lymphotropic virus type1(HTLV-1).These review articles are contributed by experts on specific viruses and their associated human cancers.Viruses account for about 20%of total human cancer cases.Although many viruses can cause various tumors in animals,only seven of them展开更多
Cyanophages are double-stranded DNA viruses that infect cyanobacteria, and they can be found in both freshwater and marine environments. They have a complex pattem of host ranges and play important roles in controllin...Cyanophages are double-stranded DNA viruses that infect cyanobacteria, and they can be found in both freshwater and marine environments. They have a complex pattem of host ranges and play important roles in controlling cyanobacteria population. Unlike marine cyanophages, for which there have been a number of recent investigations, very little attention has been paid to freshwater cyanophages. This review summarizes the taxonomy and morphology, host range, distribution, seasonal dynamics, and complete genomes of freshwater cyanophages, as well as diagnostic markers that can be used to identify them.展开更多
Rice stripe virus (RSV) infects rice and is transmitted in a propagative manner by the small brown planthopper. How RSV enters an insect cell to initiate the infection cycle is poorly understood. Sequence analysis rev...Rice stripe virus (RSV) infects rice and is transmitted in a propagative manner by the small brown planthopper. How RSV enters an insect cell to initiate the infection cycle is poorly understood. Sequence analysis revealed that the RSV NSvc2 protein was similar to the membrane glycoproteins of several members in the family Bunyaviridae and might induce cell membrane fusion. To conveniently study the membrane fusion activity of NSvc2, we constructed cell surface display vectors for expressing Nsvc2 on the insect cell surface as the membrane glycoproteins of the enveloped viruses. Our results showed that NSvc2 was successfully expressed and displayed on the surface of insect Sf9 cells. When induced by low pH, the membrane fusion was not observed in the cells that expressed NSvc2. Additionally, the membrane fusion was also not detected when co-expressing Nsvc2 and the viral capsid protein on insect cell surface. Thus, RSV NSvc2 is probably different from the phlebovirus counterparts, which could suggest different functions. RSV might enter insect cells other than by fusion with plasma or endosome membrane.展开更多
Coxsackievirus A16(CVA16),together with enterovirus type 71(EV71),is responsible for most cases of hand,foot and mouth disease(HFMD) worldwide.Recent findings suggest that the recombination between CVA16 and EV71,and ...Coxsackievirus A16(CVA16),together with enterovirus type 71(EV71),is responsible for most cases of hand,foot and mouth disease(HFMD) worldwide.Recent findings suggest that the recombination between CVA16 and EV71,and the co-circulation of these two viruses may have contributed to the increase of HFMD cases in China over the past few years.It is therefore important to further understand the virology,epidemiology,virus-host interactions and host pathogenesis of CVA16.In this study,we describe the viral kinetics of CVA16 in human rhabdomyosarcoma(RD) cells by analyzing the cytopathic effect(CPE),viral RNA replication,viral protein expression,viral RNA package and viral particle secretion in RD cells.We show that CVA16 appears to first attach,uncoat and enter into the host cell after adsorption for 1 h.Later on,CVA16 undergoes rapid replication from 3 to 6 h at MOI 1 and until 9 h at MOI 0.1.At MOI 0.1,CVA16 initiates a secondary infection as the virions were secreted before 9 h p.i.CPE was observed after 12 h p.i.,and viral antigen was first detected at 6 h p.i.at MOI 1 and at 9 h p.i.at MOI 0.1.Thus,our study provides important information for further investigation of CVA16 in order to better understand and ultimately control infections with this virus.展开更多
This paper gives a general introduction of HIV/AIDS treatment with Traditional Chinese Medicine (TCM) in China during the past 20 years. Although the role of TCM in treatment of HIV/AIDS is promising,there is still a ...This paper gives a general introduction of HIV/AIDS treatment with Traditional Chinese Medicine (TCM) in China during the past 20 years. Although the role of TCM in treatment of HIV/AIDS is promising,there is still a long way to go.展开更多
基金supported by the National Natural Science Foundation of China(32273037 and 32102636)the Guangdong Major Project of Basic and Applied Basic Research(2020B0301030007)+4 种基金Laboratory of Lingnan Modern Agriculture Project(NT2021007)the Guangdong Science and Technology Innovation Leading Talent Program(2019TX05N098)the 111 Center(D20008)the double first-class discipline promotion project(2023B10564003)the Department of Education of Guangdong Province(2019KZDXM004 and 2019KCXTD001).
文摘A switch from avian-typeα-2,3 to human-typeα-2,6 receptors is an essential element for the initiation of a pandemic from an avian influenza virus.Some H9N2 viruses exhibit a preference for binding to human-typeα-2,6 receptors.This identifies their potential threat to public health.However,our understanding of the molecular basis for the switch of receptor preference is still limited.In this study,we employed the random forest algorithm to identify the potentially key amino acid sites within hemagglutinin(HA),which are associated with the receptor binding ability of H9N2 avian influenza virus(AIV).Subsequently,these sites were further verified by receptor binding assays.A total of 12 substitutions in the HA protein(N158D,N158S,A160 N,A160D,A160T,T163I,T163V,V190T,V190A,D193 N,D193G,and N231D)were predicted to prefer binding toα-2,6 receptors.Except for the V190T substitution,the other substitutions were demonstrated to display an affinity for preferential binding toα-2,6 receptors by receptor binding assays.Especially,the A160T substitution caused a significant upregulation of immune-response genes and an increased mortality rate in mice.Our findings provide novel insights into understanding the genetic basis of receptor preference of the H9N2 AIV.
文摘Dear Editor,Historically,dipeptidyl peptidase 4(DPP4),found in alveolar regions,has been recognized as the primary receptor for several merbecoviruses like MERS-CoV(Meyerholz et al.,2016).However,angiotensin-converting enzyme 2(ACE2),highly expressed in the motile cilia of human airway epithelial cells(Sungnak et al.,2020),has been identified as the functional receptor for sarbecoviruses(e.g.,SARS-CoV-2,SARS-CoV)and setracoviruses(e.g.,HCoV-NL63).Recent studies have shown that some bat-circulating MERS-related coronaviruses(MERSr-CoVs),such as MOW15-22,PnNL2018B and HKU5,can use ACE2 to enter cells(Ma et al.,2025;Park et al.,2025).Even more worrying is that one novel bat-infecting merbecovirus HKU5-CoV lineage 2(BtHKU5-CoV-2)has been reported to use human ACE2 as a cell entry receptor(Chen et al.,2025).These ACE2-utilizing merbecoviruses expand the diversity,geographic distribution,and transmission potential of coronaviruses,posing a significant threat of spillover to humans.If an ACE2-utilizing MERSr-CoV acquire the high lethality of MERS-CoV and the high transmissibility of SARS-CoV-2 using ACE2 as a receptor,it could trigger a global pandemic with catastrophic consequences for humanity.Therefore,it is essential to evaluate serological cross-reactivity in sera from SARS-CoV-2-infected individuals against ACE2-using MERSr-CoVs,and urgent to develop preventive vaccines and pan-coronavirus antivirals confront the potential threat(Jiang and Wu,2025).
基金the Ethics Committee of Guangzhou Eighth People's Hospital(202033166),and all participants provided written informed consent.
文摘Some HIV-infected individuals receiving ART develop low-level viremia(LLV),with a plasma viral load of 50-1000 copies/mL.Persistent low-level viremia is associated with subsequent virologic failure.The peripheral blood CD4^(+)T cell pool is a source of LLV.However,the intrinsic characteristics of CD4^(+)T cells in LLV which may contribute to low-level viremia are largely unknown.We analyzed the transcriptome profiling of peripheral blood CD4^(+)T cells from healthy controls(HC)and HIV-infected patients receiving ART with either virologic sup-pression(VS)or LLV.To identify pathways potentially responding to increasing viral loads from HC to VS and to LLV,KEGG pathways of differentially expressed genes(DEGs)were acquired by comparing VS with HC(VS-HC group)and LLV with VS(LLV-VS group),and overlapped pathways were analyzed.Characterization of DEGs in key overlapping pathways showed that CD4^(+)T cells in LLV expressed higher levels of Th1 signature transcription factors(TBX21),toll-like receptors(TLR-4,-6,-7 and-8),anti-HIV entry chemokines(CCL3 and CCL4),and anti-IL-1βfactors(ILRN and IL1R2)compared to VS.Our results also indicated activation of the NF-κB and TNF signaling pathways that could promote HIV-1 transcription.Finally,we evaluated the effects of 4 and 17 tran-scription factors that were upregulated in the VS-HC and LLV-VS groups,respectively,on HIV-1 promoter activity.Functional studies revealed that CXXC5 significantly increased,while SOX5 markedly suppressed HIV-1 tran-scription.In summary,we found that CD4^(+)T cells in LLV displayed a distinct mRNA profiling compared to that in VS,which promoted HIV-1 replication and r+eactivation of viral latency and may eventually contribute to virologic failure in patients with persistent LLV.CXXC5 and SOX5 may serve as targets for the development of latency-reversing agents.
基金supported by National Natural Science Foundation of China(No.82104134)Key Technology Research and Development Program of Shandong,China(No.2020CXGC010505)The Social Benefiting Technology Program of Qingdao,China(No.21-1-4-rkjk-15-nsh).
文摘Influenza A virus(IAV)genome comprises eight negative-sense RNA segments,of which the replication is well orchestrated and the delicate balance of multiple segments are dynamically regulated throughout IAV life cycle.However,previous studies seldom discuss these balances except for functional hemagglutinin-neuraminidase balance that is pivotal for both virus entry and release.Therefore,we attempt to revisit IAV life cycle by highlighting the critical role of“genome balance”.Moreover,we raise a“balance regression”model of IAV evolution that the virus evolves to rebalance its genome after reassortment or interspecies transmission,and direct a“balance compensation”strategy to rectify the“genome imbalance”as a result of artificial modifications during creation of recombinant IAVs.This review not only improves our understanding of IAV life cycle,but also facilitates both basic and applied research of IAV in future.
基金funded by the National Key Research and Development Programs of China(No.2022YFC2603800)Jiangsu Provincial Key Research and Development Projects(No.BE2017693).
文摘Ticks are considered the second most common pathogen vectors transmitting a broad range of vital human and veterinary viruses.From 2017 to 2018,640 ticks were collected in eight different provinces in central and western China.Six species were detected,including H.longicornis,De.everestianus,Rh.microplus,Rh.turanicus,Rh.sanguineous,and Hy.asiaticum.Sixty-four viral metagenomic libraries were constructed on the MiSeq Illumina platform,resulting in 13.44 G(5.88×10^(7))of 250-bp-end reads,in which 2,437,941 are viral reads.We found 27 nearly complete genome sequences,including 16 genome sequences encoding entire protein-coding regions(lack of 30 or 50 end non-coding regions)and complete viral genomes,distributed in the arboviral family(Chuviridae,Rhabdoviridae,Nairoviridae,Phenuiviridae,Flaviviridae,Iflaviridae)as well as Parvoviridae and Polyomaviridae that cause disease in mammals and even humans.In addition,13 virus sequences found in Chuviridae,Nairoviridae,Flaviviridae,Iflaviridae,Hepeviridae,Parvoviridae,and Polyomaviridae were identified as belonging to a new virus species in the identified viral genera.Besides,an epidemiological survey shows a high prevalence(9.38%and 15.63%)of two viruses(Ovine Copiparvovirus and Bovine parvovirus 2)in the tick cohort.
基金grant of National Key Research and Development Program of China(2022YFC3400700)National Natural Science Foundation of China(Nos.82241034,82370397,31971358,U22A20266 and C-0052)+2 种基金Top-Notch Talent Program of Hubei Province and Tongji Hospital(No.2021YBJRC005)Hubei Provincial Key Research and Developmental Program(2022BCA037)Hubei Provincial Natural Science Foundation of China(2017CFB536).
文摘Myocardial injury is one of the most common comorbidity in SARS-CoV-2 infected patients,and has poor prognosis.However,the incidence of myocardial injury in patients with SARS-CoV-2 infection has not been sufficiently investigated during the Omicron wave.We conducted a retrospective study of 2690 patients with confirmed SARS-CoV-2 Omicron infection from Tongji Hospital.The results indicated that the myocardial injury accounted for 30.8%of the total patients with SARS-CoV-2 infection and was associated with higher in-hospital mortality than those without injury before and after propensity score matching(PSM)[adjusted hazard ratio(HR),10.61;95%confidence interval(CI),7.76–14.51;P<0.001;adjusted HR,2.70;95%CI,1.86–3.93;P<0.001;respectively].Further,the levels of cytokines(IL-1β,IL-6,IL-10,and TNF-α)in patients with myocardial injury were higher than those without injury,and the higher levels of cytokines in the myocardial injury group were associated with increased mortality.Administration of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers(ACEI/ARB)could significantly reduce the mortality in patients with myocardial injury(adjusted HR,0.52;95%CI,0.38–0.71;P<0.001).Additionally,the level of angiotensin II increased in patients with SARS-CoV-2 infection was even higher in myocardial injury group compared to those without injury.Collectively,the study summarized the clinical characteristic and outcome of SARS-CoV-2 infected patients with myocardial injury during the Omicron wave in China,and validated the protective role of ACEI/ARB in improving the survival of those with myocardial injury.
基金supported by the National Major Science Program Foundation(No.JK2020NC017&2018ZX10711001-003)the Scientific Research Projects of the General Administration of Customs(No.2019HK042)
文摘Dear Editor,Severe acute respiratory syndrome coronavirus-2(SARS-Co V-2)is a novel coronavirus that causes the outbreak of coronavirus disease 2019(COVID-19)(Li et al.,2020a).Viral nucleic acid testing is the standard method for the laboratory diagnosis of COVID-19(Wu et al.,2020a;Zhu et al.,2020).Currently,a variety of qPCR-based detection kits are used for laboratory-based detection and confirmation of SARS-CoV-2 infection(Corman et al.,2020;Hussein et al.,2020;Ruhan et al.,2020;Veyer et al.,2020).Conventional qPCR involves virus inactivation,nucleic acid extraction,and qPCR amplification procedures.Therefore,the process is complicated,which usually takes longer than 2 h,and requires biosafety laboratories and professional staff.Thus,qPCR is not suitable for use in field or medical units.
基金supported by the following grants:the National Key R&D Program of China(Grant 2016YFC1201000 to X.J.)the Institute Fund of Shanghai Public Health Clinical Center(Grant KY-GW-2021-17 to ZH.L.)。
文摘Arthropod-borne chikungunya virus(CHIKV)infection can cause a debilitating arthritic disease in human.However,there are no specific antiviral drugs and effective licensed vaccines against CHIKV available for clinical use.Here,we developed an m RNA-lipid nanoparticle(m RNA-LNP)vaccine expressing CHIKV E2-E1 antigen,and compared its immunogenicity with soluble recombinant protein s E2-E1 antigen expressed in S2 cells.For comparison,we first showed that recombinant protein antigens mixed with aluminum adjuvant elicit strong antigenspecific humoral immune response and a moderate cellular immune response in C57BL/6 mice.Moreover,s E2-E1vaccine stimulated 12-23 folds more neutralizing antibodies than s E1 vaccine and s E2 vaccine.Significantly,when E2-E1 gene was delivered by an m RNA-LNP vaccine,not only the better magnitude of neutralizing antibody responses was induced,but also greater cellular immune responses were generated,especially for CD8+T cell responses.Moreover,E2-E1-LNP induced CD8~+T cells can perform cytotoxic effect in vivo.Considering its better immunogenicity and convenience of preparation,we suggest that more attention should be placed to develop CHIKV E2-E1-LNP m RNA vaccine.
基金We thank National Infrastructure of Microbial Resources(NIMR-2014-3)for providing valuable reagentsThis work was supported by the National Mega-Project for Infectious Disease(2018ZX10301408 SC)+4 种基金the National Key Research and Development program of China(2018YFE0107600 SC)the National Natural Science Foundation of China(81903679 LM)the National Natural Science Foundation of China(81772205 SC)Peking Union Medical College Youth Fund(332017075 LM)CAMS innovation fund for Medical Sciences(2018-I2M-3-004 SC).
文摘The CREB-regulated transcriptional co-activators(CRTCs),including CRTC1,CRTC2 and CRTC3,enhance transcription of CREB-targeted genes.In addition to regulating host gene expression in response to cAMP,CRTCs also increase the infection of several viruses.While human immunodeficiency virus type 1(HIV-1)long terminal repeat(LTR)promoter harbors a cAMP response element and activation of the cAMP pathway promotes HIV-1 transcription,it remains unknown whether CRTCs have any effect on HIV-1 transcription and HIV-1 infection.Here,we reported that CRTC2 expression was induced by HIV-1 infection,but CRTC2 suppressed HIV-1 infection and diminished viral RNA expression.Mechanistic studies revealed that CRTC2 inhibited transcription from HIV-1 LTR and diminished RNA PolⅡoccupancy at the LTR independent of its association with CREB.Importantly,CRTC2 inhibits the activation of latent HIV-1.Together,these data suggest that in response to HIV-1 infection,cells increase the expression of CRTC2 which inhibits HIV-1 gene expression and may play a role in driving HIV-1 into latency.
基金supported by grants from National Major Science&Technology Project for Control and Prevention of Major Infectious Diseases in China(2018ZX10201002-009-005)。
文摘Dear Editor,Acute gastroenteritis(AGE)is a leading infectious cause of morbidity worldwide,particularly among children in developing countries(Mortality and Causes of Death2016).With the introduction of rotavirus vaccines,noroviruses have been identified as a leading cause of AGE outbreaks and sporadic disease worldwide(Hall et al.
基金supported by Dr.Wu Lien-Teh Scientific Funds of Harbin Medical University。
文摘Infectious diseases pose a serious threat to human health and affect social,economic,and cultural development.Many infectious diseases,such as severe acute respiratory syndrome(SARS,2013),Middle East respiratory syndrome(MERS,2012 and 2013),Zika virus infection(2007,2013 and 2015),and coronavirus disease 2019(COVID-19,2019),have occurred as regional or global epidemics(Reperant and Osterhaus 2017;Gao 2018)。
基金grants from Beijing Natural Science Foundation(No.19G10290)National Natural Science Foundation of China(No.81772184).
文摘Enterovirus A71(EV-A71) is the major pathogen responsible for the severe hand, foot and mouth disease worldwide, for which few effective antiviral drugs are presently available. Interferon-a(IFN-a) has been used in antiviral therapy for decades;it has been reported that EV-A71 antagonizes the antiviral activity of IFN-a based on viral 2 Apro-mediated reduction of the interferon-alpha receptor 1(IFNAR1);however, the mechanism remains unknown. Here, we showed a significant increase in IFNAR1 protein induced by IFN-a in RD cells, whereas EV-A71 infection caused obvious downregulation of the IFNAR1 protein and blockage of IFN-a signaling. Subsequently, we observed that EV-A71 2 Apro inhibited IFNAR1 translation by cleavage of the eukaryotic initiation factor 4 GI(eIF4GI), without affecting IFNAR1 m RNA levels induced by IFN-a. The inhibition of IFNAR1 translation also occurred in puromycin-induced apoptotic cells when caspase-3 cleaved e IF4 GI. Importantly, we verified that 2 Aprocould activate cellular caspase-3, which was subsequently involved in e IF4 GI cleavage mediated by 2 Apro. Furthermore, inhibition of caspase-3 activation resulted in the partial restoration of IFNAR1 in cells transfected with 2 A or infected with EV-A71, suggesting the pivotal role of both viral 2 Aproand caspase-3 activation in the disturbance of IFN-a signaling. Collectively, we elucidate a novel mechanism by which cellular caspase-3 contributes to viral 2 Apro-mediated down-regulation of IFNAR1 at the translation level during EV-A71 infection, indicating that caspase-3 inhibition could be a potential complementary strategy to improve clinical anti-EV-A71 therapy with IFN-a.
基金funded by the National Natural Science Foundation of China (Grant No.81290341)
文摘Dear Editor,The hepatitis A virus(HAV)is a common agent causing acute liver disease worldwide,with approximately 11,000deaths annually(WHO 2017).The virus is transmitted primarily by the fecal-oral route and it normally infects people living in high-density and resource-poor
基金supported by the Natural Science Foundation of Shanghai (17ZR1401400)the Natural Science Foundation of China (grant no. 81772170, U603117)the Doctoral Fund of Ministry of Education of China (Grant No. 20120071120050)
文摘Intravenous drug users(IDUs) have been demonstrated to be highly vulnerable to HIV/AIDS.Nevertheless, the prevalence of Kaposi's sarcoma associated herpesvirus(KSHV), an important co-infected agent with HIV, among this population remained obscure. We conducted a systematic review on the epidemiological features of KSHV among IDUs worldwide. Eligible studies were retrieved from 6 electronic databases(Pub Med, EMBASE, Web of Science, CBM, CNKI and Wanfang).We calculated the pooled prevalence and 95% confidence interval(CI) overall and among subgroups using either random-effects model or fixed-effects model depending on between-study heterogeneity. The potential publication bias was assessed by the Egger's test. A meta-regression analysis was performed to explore the sources of heterogeneity. Finally, twenty-two studies with a total sample of 7881 IDUs were included in the analysis. The pooled prevalence of KSHV was14.71%(95% CI 11.12%–19.46%) among IDUs. Specifically, KSHV prevalence was 10.86%(95% CI6.95%–16.96%) in HIV-negative IDUs, and 13.56%(95% CI 10.57%–17.38%) in HIV-positive IDUs.Moreover, prevalence among IDUs from the three continents involved in the current study was similar:16.10%(95%CI 7.73%–33.54%) in Asia; 14.22%(95%CI 8.96%–22.57%) in Europe and 14.06%(95%CI11.38%–17.37%) in America. Globally, IDUs are at higher risk of the KSHV infection when compared with the general population, regardless of geographical region or HIV-infection status.
基金supported by Nature Science Foundation of China (NSFC 81130082)NIH grants AI097318 and AI091953supported by NIH grants DK094652,DK100257 and CA177337
文摘This special issue of the journal is dedicated to the important topic of oncogenic viruses and cancer.It contains seven review articles covering all known oncogenic viruses except for human T-lymphotropic virus type1(HTLV-1).These review articles are contributed by experts on specific viruses and their associated human cancers.Viruses account for about 20%of total human cancer cases.Although many viruses can cause various tumors in animals,only seven of them
文摘Cyanophages are double-stranded DNA viruses that infect cyanobacteria, and they can be found in both freshwater and marine environments. They have a complex pattem of host ranges and play important roles in controlling cyanobacteria population. Unlike marine cyanophages, for which there have been a number of recent investigations, very little attention has been paid to freshwater cyanophages. This review summarizes the taxonomy and morphology, host range, distribution, seasonal dynamics, and complete genomes of freshwater cyanophages, as well as diagnostic markers that can be used to identify them.
基金Natural Science Foundation of China Grants (30970138)the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Rice stripe virus (RSV) infects rice and is transmitted in a propagative manner by the small brown planthopper. How RSV enters an insect cell to initiate the infection cycle is poorly understood. Sequence analysis revealed that the RSV NSvc2 protein was similar to the membrane glycoproteins of several members in the family Bunyaviridae and might induce cell membrane fusion. To conveniently study the membrane fusion activity of NSvc2, we constructed cell surface display vectors for expressing Nsvc2 on the insect cell surface as the membrane glycoproteins of the enveloped viruses. Our results showed that NSvc2 was successfully expressed and displayed on the surface of insect Sf9 cells. When induced by low pH, the membrane fusion was not observed in the cells that expressed NSvc2. Additionally, the membrane fusion was also not detected when co-expressing Nsvc2 and the viral capsid protein on insect cell surface. Thus, RSV NSvc2 is probably different from the phlebovirus counterparts, which could suggest different functions. RSV might enter insect cells other than by fusion with plasma or endosome membrane.
基金Partly supported by the National Natural Science Foundation of China (No. 20872048)
文摘Coxsackievirus A16(CVA16),together with enterovirus type 71(EV71),is responsible for most cases of hand,foot and mouth disease(HFMD) worldwide.Recent findings suggest that the recombination between CVA16 and EV71,and the co-circulation of these two viruses may have contributed to the increase of HFMD cases in China over the past few years.It is therefore important to further understand the virology,epidemiology,virus-host interactions and host pathogenesis of CVA16.In this study,we describe the viral kinetics of CVA16 in human rhabdomyosarcoma(RD) cells by analyzing the cytopathic effect(CPE),viral RNA replication,viral protein expression,viral RNA package and viral particle secretion in RD cells.We show that CVA16 appears to first attach,uncoat and enter into the host cell after adsorption for 1 h.Later on,CVA16 undergoes rapid replication from 3 to 6 h at MOI 1 and until 9 h at MOI 0.1.At MOI 0.1,CVA16 initiates a secondary infection as the virions were secreted before 9 h p.i.CPE was observed after 12 h p.i.,and viral antigen was first detected at 6 h p.i.at MOI 1 and at 9 h p.i.at MOI 0.1.Thus,our study provides important information for further investigation of CVA16 in order to better understand and ultimately control infections with this virus.
文摘This paper gives a general introduction of HIV/AIDS treatment with Traditional Chinese Medicine (TCM) in China during the past 20 years. Although the role of TCM in treatment of HIV/AIDS is promising,there is still a long way to go.
