The World Health Organization has declared the present Zika virus epidemic to be a ＇Public Health Emergency of International Concern＇. The virus appears to have spread from Thailand to French Polynesia in 2013, and ...The World Health Organization has declared the present Zika virus epidemic to be a ＇Public Health Emergency of International Concern＇. The virus appears to have spread from Thailand to French Polynesia in 2013, and has since infected over a million people in the countries of South and Central America. In most cases the infection is mild and transient, but the virus does appear to be strongly neurotropic and the presumptive cause of both birth defects in fetuses and Guillain-Barr6 syndrome in some adults. In this paper, the techniques and utilities developed in the study of mitochondrial DNA were applied to the Zika virus. As a result, it is possible to show in a simple manner how a phylogenetic tree may be constructed and how the mutation rate of the virus can be measured. The study showed the mutation rate to vary between 12 and 25 bases a year, in a viral genome of 10 272 bases. This rapid mutation rate will enable the geographic spread of the epidemic to be monitored easily and may also prove useful in assisting the identification of preventative measures that are working, and those that are not.展开更多
A total of 288 grapevine samples of 61 different grapevine cultivars,collected from 22 provinces and regions,were analyzed by reverse transcription-PCR(RT-PCR) for the presence of grapevine fabavirus(GFabV).PCR detect...A total of 288 grapevine samples of 61 different grapevine cultivars,collected from 22 provinces and regions,were analyzed by reverse transcription-PCR(RT-PCR) for the presence of grapevine fabavirus(GFabV).PCR detection results showed the incidences of GFabV were 12.8%(30/235) and 48.1%(25/52) in the asymptomatic and symptomatic vines,respectively.The genetic diversity of GFabV isolates was analyzed based on partial nucleotide and encoded amino acid sequences of the RNA1 and RNA2 polyprotein genes.Phylogenetic analyses of the RNA1 and RNA2 gene sequences divided the GFabV isolates into five well-defined groups.Groups 1,2,and 4 comprised only Chinese isolates.This article represents the first report for the prevalence and genetic diversity of GFabV in grapevines grown in China.展开更多
Proteolytic processing of viral polyproteins is indispensible for the lifecycle of coronaviruses.The main protease(M^(pro))of SARS-CoV is an attractive target for anti-SARS drug development as it is essential for the ...Proteolytic processing of viral polyproteins is indispensible for the lifecycle of coronaviruses.The main protease(M^(pro))of SARS-CoV is an attractive target for anti-SARS drug development as it is essential for the polyprotein processing.M^(pro) is initially produced as part of viral polyproteins and it is matured by autocleavage.Here,we report that,with the addition of an N-terminal extension peptide,M^(pro) can form a domain-swapped dimer.After complete removal of the extension peptide from the dimer,the mature M^(pro) self-assembles into a novel super-active octamer(AO-M^(pro)).The crystal structure of AO-M^(pro) adopts a novel fold with four domainswapped dimers packing into four active units with nearly identical conformation to that of the previously reported M^(pro) active dimer,and 3D domain swapping serves as a mechanism to lock the active conformation due to entanglement of polypeptide chains.Compared with the previously well characterized form of M^(pro),in equilibrium between inactive monomer and active dimer,the stable AO-M^(pro) exhibits much higher proteolytic activity at low concentration.As all eight active sites are bound with inhibitors,the polyvalent nature of the interaction between AO-M^(pro) and its polyprotein substrates with multiple cleavage sites,would make AO-M^(pro) functionally much more superior than the M^(pro) active dimer for polyprotein processing.Thus,during the initial period of SARS-CoV infection,this novel active form AOM^(pro) should play a major role in cleaving polyproteins as the protein level is extremely low.The discovery of AOM^(pro) provides new insights about the functional mechanism of M^(pro) and its maturation process.展开更多
A complex network of cellular receptors,RNA targeting pathways,and small-molecule signaling provides robust plant immunity and tolerance to viruses.To maximize their fitness,viruses must evolve control mechanisms to b...A complex network of cellular receptors,RNA targeting pathways,and small-molecule signaling provides robust plant immunity and tolerance to viruses.To maximize their fitness,viruses must evolve control mechanisms to balance host immune evasion and plant-damaging effects.The genus Potyvirus comprises plant viruses characterized by RNA genomes that encode large polyproteins led by the P1 protease.A P1 autoinhibitory domain controls polyprotein processing,the release of a downstream functional RNAsilencing suppressor,and viral replication.Here,we show that P1Pro,a plum pox virus clone that lacks the P1 autoinhibitory domain,triggers complex reprogramming of the host transcriptome and high levels of abscisic acid(ABA)accumulation.A meta-analysis highlighted ABA connections with host pathways known to control RNA stability,turnover,maturation,and translation.Transcriptomic changes triggered by P1Pro infection or ABA showed similarities in host RNA abundance and diversity.Genetic and hormone treatment assays showed that ABA promotes plant resistance to potyviral infection.Finally,quantitative mathematical modeling of viral replication in the presence of defense pathways supported self-control of polyprotein processing kinetics as a viral mechanism that attenuates the magnitude of the host antiviral response.Overall,our findings indicate that ABA is an active player in plant antiviral immunity,which is nonetheless evaded by a self-controlled RNA virus.展开更多
文摘The World Health Organization has declared the present Zika virus epidemic to be a ＇Public Health Emergency of International Concern＇. The virus appears to have spread from Thailand to French Polynesia in 2013, and has since infected over a million people in the countries of South and Central America. In most cases the infection is mild and transient, but the virus does appear to be strongly neurotropic and the presumptive cause of both birth defects in fetuses and Guillain-Barr6 syndrome in some adults. In this paper, the techniques and utilities developed in the study of mitochondrial DNA were applied to the Zika virus. As a result, it is possible to show in a simple manner how a phylogenetic tree may be constructed and how the mutation rate of the virus can be measured. The study showed the mutation rate to vary between 12 and 25 bases a year, in a viral genome of 10 272 bases. This rapid mutation rate will enable the geographic spread of the epidemic to be monitored easily and may also prove useful in assisting the identification of preventative measures that are working, and those that are not.
基金supported by the National Key R&D Program of China(2018YFD0201301)the earmarked fund for the China Agriculture Research System(CARS-29-bc-1)the Fundamental Research Funds for Central Non-profit Scientific Institutions,China
文摘A total of 288 grapevine samples of 61 different grapevine cultivars,collected from 22 provinces and regions,were analyzed by reverse transcription-PCR(RT-PCR) for the presence of grapevine fabavirus(GFabV).PCR detection results showed the incidences of GFabV were 12.8%(30/235) and 48.1%(25/52) in the asymptomatic and symptomatic vines,respectively.The genetic diversity of GFabV isolates was analyzed based on partial nucleotide and encoded amino acid sequences of the RNA1 and RNA2 polyprotein genes.Phylogenetic analyses of the RNA1 and RNA2 gene sequences divided the GFabV isolates into five well-defined groups.Groups 1,2,and 4 comprised only Chinese isolates.This article represents the first report for the prevalence and genetic diversity of GFabV in grapevines grown in China.
基金This work was supported by Grant No.2003CB514104 from the National Basic Research Program(973 Program)Grant No.30125009 from National Natural Science Foundation of China to Bin Xia+1 种基金Grant No.2006AA02A323 from the National Programs for High Technology Research and Development Program(863 Program)to Changwen JinGrant No.2009ZX09311-001 to Zhiyong Lou from the National Major Projects of China.
文摘Proteolytic processing of viral polyproteins is indispensible for the lifecycle of coronaviruses.The main protease(M^(pro))of SARS-CoV is an attractive target for anti-SARS drug development as it is essential for the polyprotein processing.M^(pro) is initially produced as part of viral polyproteins and it is matured by autocleavage.Here,we report that,with the addition of an N-terminal extension peptide,M^(pro) can form a domain-swapped dimer.After complete removal of the extension peptide from the dimer,the mature M^(pro) self-assembles into a novel super-active octamer(AO-M^(pro)).The crystal structure of AO-M^(pro) adopts a novel fold with four domainswapped dimers packing into four active units with nearly identical conformation to that of the previously reported M^(pro) active dimer,and 3D domain swapping serves as a mechanism to lock the active conformation due to entanglement of polypeptide chains.Compared with the previously well characterized form of M^(pro),in equilibrium between inactive monomer and active dimer,the stable AO-M^(pro) exhibits much higher proteolytic activity at low concentration.As all eight active sites are bound with inhibitors,the polyvalent nature of the interaction between AO-M^(pro) and its polyprotein substrates with multiple cleavage sites,would make AO-M^(pro) functionally much more superior than the M^(pro) active dimer for polyprotein processing.Thus,during the initial period of SARS-CoV infection,this novel active form AOM^(pro) should play a major role in cleaving polyproteins as the protein level is extremely low.The discovery of AOM^(pro) provides new insights about the functional mechanism of M^(pro) and its maturation process.
基金supported by funds to J.A.G.from the Ministerio de Ciencia e Innovaciòn(Spain),grants BIO2016-80572-R and PID2019-109380RBI00/AEI/10.13039/501100011033(AEI-FEDER)funded by grant K124705 from the National Research Development and Innovation Office(Hungary)+2 种基金S.M.-B.by grant 2017 SGR 980 from the Generalitat de Catalunya(Spain)supported by NIH grant HG006620the recipient of a post-doctoral fellowship from Academia Sinica(Taiwan).
文摘A complex network of cellular receptors,RNA targeting pathways,and small-molecule signaling provides robust plant immunity and tolerance to viruses.To maximize their fitness,viruses must evolve control mechanisms to balance host immune evasion and plant-damaging effects.The genus Potyvirus comprises plant viruses characterized by RNA genomes that encode large polyproteins led by the P1 protease.A P1 autoinhibitory domain controls polyprotein processing,the release of a downstream functional RNAsilencing suppressor,and viral replication.Here,we show that P1Pro,a plum pox virus clone that lacks the P1 autoinhibitory domain,triggers complex reprogramming of the host transcriptome and high levels of abscisic acid(ABA)accumulation.A meta-analysis highlighted ABA connections with host pathways known to control RNA stability,turnover,maturation,and translation.Transcriptomic changes triggered by P1Pro infection or ABA showed similarities in host RNA abundance and diversity.Genetic and hormone treatment assays showed that ABA promotes plant resistance to potyviral infection.Finally,quantitative mathematical modeling of viral replication in the presence of defense pathways supported self-control of polyprotein processing kinetics as a viral mechanism that attenuates the magnitude of the host antiviral response.Overall,our findings indicate that ABA is an active player in plant antiviral immunity,which is nonetheless evaded by a self-controlled RNA virus.
