Dear Editor,Since the global eradication of smallpox in the 1980s,monkeypox has become the most severe infectious disease caused by pathogenic orthopoxvirus(OPXV)infection.Monkeypox virus(MPXV)is the causative pathoge...Dear Editor,Since the global eradication of smallpox in the 1980s,monkeypox has become the most severe infectious disease caused by pathogenic orthopoxvirus(OPXV)infection.Monkeypox virus(MPXV)is the causative pathogen of monkeypox and was classified as a category of human infectious pathogen by theMinistry of Health of the People's Republic ofChina in 2006.Monkeypox has traditionally been endemic in West and Central Africa since it was discovered nearly 70 years ago(Breman et al.,1980).However,beginning in early May 2022,a sudden outbreak of monkeypox has taken place and remains ongoing in more than 100 nonendemic countries and territories located at Europe,Americas,and Asia(https://worldhealthorg.shinyapps.io/mpx_global/).展开更多
Several variants of concern(VOCs)have emerged since the WIV04 strain of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was first isolated in January 2020.Due to mutations in the spike(S)protein,these VOCs ...Several variants of concern(VOCs)have emerged since the WIV04 strain of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was first isolated in January 2020.Due to mutations in the spike(S)protein,these VOCs have evolved to enhance viral infectivity and immune evasion.However,whether mutations of the other viral proteins lead to altered viral propagation and drug resistance remains obscure.The replicon is a noninfectious viral surrogate capable of recapitulating certain steps of the viral life cycle.Although several SARS-CoV-2 replicons have been developed,none of them were derived from emerging VOCs and could only recapitulate viral genome replication and subgenomic RNA(sgRNA)transcription.In this study,SARS-CoV-2 replicons derived from the WIV04 strain and two VOCs(the Beta and Delta variants)were prepared by removing the S gene from their genomes,while other structural genes remained untouched.These replicons not only recapitulate viral genome replication and sgRNA transcription but also support the assembly and release of viral-like particles,as manifested by electron microscopic assays.Thus,the S-deletion replicon could recapitulate virtually all the post-entry steps of the viral life cycle and provides a versatile tool for measuring viral intracellular propagation and screening novel antiviral drugs,including inhibitors of virion assembly and release.Through the quantification of replicon RNA released into the supernatant,we demonstrate that viral intracellular propagation and drug response to remdesivir have not yet substantially changed during the evolution of SARS-CoV-2 from the WIV04 strain to the Beta and Delta VOCs.展开更多
Orthopoxviruses(OPXVs)belong to a group of nucleo-cytoplasmic large DNA viruses.Human pathogenic OPXVs(hpOPXVs)include at least five viruses,among which smallpox virus and monkeypox virus are the most dangerous viral ...Orthopoxviruses(OPXVs)belong to a group of nucleo-cytoplasmic large DNA viruses.Human pathogenic OPXVs(hpOPXVs)include at least five viruses,among which smallpox virus and monkeypox virus are the most dangerous viral pathogens.Both viruses are classified as category-one human infectious pathogens in China.Although smallpox was globally eradicated in the 1980 s,it is still a top biosecurity threat owing to the possibility of either being leaked to the outside world from a laboratory or being weaponized by terrorists.Beginning in early May 2022,a sudden outbreak of monkeypox was concurrently reported in more than 100 disparate geographical areas,representing a public health emergency of international concern,as declared by the World Health Organization(WHO).In this review,we present the reasons for hpOPXVs such as monkeypox virus presenting a potential threat to public health.We then systematically review the historical and recent development of vaccines and drugs against smallpox and monkeypox.In the final section,we highlight the importance of viromics studies as an integral part of a forward defense strategy to eliminate the potential threat to public health from emerging or re-emerging hpOPXVs and their variants.展开更多
DearEditor,The Arenaviridae family(recently assigned to the Bunyavirales order)is a group of emerging viruses that include causative agents of severe hemorrhagic fevers with high mortality in humans(de la Torre,2009)....DearEditor,The Arenaviridae family(recently assigned to the Bunyavirales order)is a group of emerging viruses that include causative agents of severe hemorrhagic fevers with high mortality in humans(de la Torre,2009).Lymphocytic choriomeningitis virus(LCMV)is the prototypic member of the Arenaviridae family and belongs to the Old World(OW)arenavirus together with Lassa virus(LASV),which are distinct from the New World(NW)arenavirus[e.g.Machupo virus(MACV)and Junin virus(JUNV)].LCMV infection in the fetus and newborm results in severe impairment of brain development associated with sensory loss and mental retardation and is also known to be associated with severe systemic infection with high mortality in transplantation patients(Palacios et al.,2008).展开更多
Dear Editor,Tremendous efforts have been made globally to develop therapeutics and prophylactics against severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)which has caused thousands of millions of infections ...Dear Editor,Tremendous efforts have been made globally to develop therapeutics and prophylactics against severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)which has caused thousands of millions of infections and deaths worldwide.A series of potent neutralizing antibodies with defined epitopes targeting RBD have been recently identified with different strategies.However,being an RNA virus,the instability of the SARS-CoV-2 genome results in numerous S-protein variants with altered viral phenotypes.展开更多
基金supported by the National Science and Technology Major Project of China(2018ZX10711001-006).
文摘Dear Editor,Since the global eradication of smallpox in the 1980s,monkeypox has become the most severe infectious disease caused by pathogenic orthopoxvirus(OPXV)infection.Monkeypox virus(MPXV)is the causative pathogen of monkeypox and was classified as a category of human infectious pathogen by theMinistry of Health of the People's Republic ofChina in 2006.Monkeypox has traditionally been endemic in West and Central Africa since it was discovered nearly 70 years ago(Breman et al.,1980).However,beginning in early May 2022,a sudden outbreak of monkeypox has taken place and remains ongoing in more than 100 nonendemic countries and territories located at Europe,Americas,and Asia(https://worldhealthorg.shinyapps.io/mpx_global/).
基金supported by grants from the National Key Research and Development Project of China (2020YFC0845900)the China Postdoctoral Science Foundation (2020T130021ZX,2021M693198)
文摘Several variants of concern(VOCs)have emerged since the WIV04 strain of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was first isolated in January 2020.Due to mutations in the spike(S)protein,these VOCs have evolved to enhance viral infectivity and immune evasion.However,whether mutations of the other viral proteins lead to altered viral propagation and drug resistance remains obscure.The replicon is a noninfectious viral surrogate capable of recapitulating certain steps of the viral life cycle.Although several SARS-CoV-2 replicons have been developed,none of them were derived from emerging VOCs and could only recapitulate viral genome replication and subgenomic RNA(sgRNA)transcription.In this study,SARS-CoV-2 replicons derived from the WIV04 strain and two VOCs(the Beta and Delta variants)were prepared by removing the S gene from their genomes,while other structural genes remained untouched.These replicons not only recapitulate viral genome replication and sgRNA transcription but also support the assembly and release of viral-like particles,as manifested by electron microscopic assays.Thus,the S-deletion replicon could recapitulate virtually all the post-entry steps of the viral life cycle and provides a versatile tool for measuring viral intracellular propagation and screening novel antiviral drugs,including inhibitors of virion assembly and release.Through the quantification of replicon RNA released into the supernatant,we demonstrate that viral intracellular propagation and drug response to remdesivir have not yet substantially changed during the evolution of SARS-CoV-2 from the WIV04 strain to the Beta and Delta VOCs.
基金This work was supported by the National Science and Technology Major Project of China(2018ZX10711001-006).
文摘Orthopoxviruses(OPXVs)belong to a group of nucleo-cytoplasmic large DNA viruses.Human pathogenic OPXVs(hpOPXVs)include at least five viruses,among which smallpox virus and monkeypox virus are the most dangerous viral pathogens.Both viruses are classified as category-one human infectious pathogens in China.Although smallpox was globally eradicated in the 1980 s,it is still a top biosecurity threat owing to the possibility of either being leaked to the outside world from a laboratory or being weaponized by terrorists.Beginning in early May 2022,a sudden outbreak of monkeypox was concurrently reported in more than 100 disparate geographical areas,representing a public health emergency of international concern,as declared by the World Health Organization(WHO).In this review,we present the reasons for hpOPXVs such as monkeypox virus presenting a potential threat to public health.We then systematically review the historical and recent development of vaccines and drugs against smallpox and monkeypox.In the final section,we highlight the importance of viromics studies as an integral part of a forward defense strategy to eliminate the potential threat to public health from emerging or re-emerging hpOPXVs and their variants.
基金facility support.This work was supported by the National Natural Science Foundation of China(32188101 and U20A20135)the National Program on Key Research Project of China(2020YFA0707500),and Tsinghua University Spring Breeze Fund.
文摘DearEditor,The Arenaviridae family(recently assigned to the Bunyavirales order)is a group of emerging viruses that include causative agents of severe hemorrhagic fevers with high mortality in humans(de la Torre,2009).Lymphocytic choriomeningitis virus(LCMV)is the prototypic member of the Arenaviridae family and belongs to the Old World(OW)arenavirus together with Lassa virus(LASV),which are distinct from the New World(NW)arenavirus[e.g.Machupo virus(MACV)and Junin virus(JUNV)].LCMV infection in the fetus and newborm results in severe impairment of brain development associated with sensory loss and mental retardation and is also known to be associated with severe systemic infection with high mortality in transplantation patients(Palacios et al.,2008).
基金supported by ShanghaiTech,Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at ShanghaiTech University(G.Z.),and grants from the National Key Research and Development Program of China[Grant Nos.2017YFC1001301(G.Z.),2019YFA0111001(H.W.)]the National Natural Science Foundation of China[Nos.31670919(H.W.),81822045(L.L.)]+1 种基金Lingang Laboratory(No.LG202101-01-07 to X.Y.),Program of Shanghai Academic/Technology Research Leader[20XD1420300(L.L.)]Emergency response to new coronavirus infection scientific and technological project[YD9110002004(J.W.)],and Shanghai Sailing Program[20YF1430900(S.-M.Z.)].
文摘Dear Editor,Tremendous efforts have been made globally to develop therapeutics and prophylactics against severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)which has caused thousands of millions of infections and deaths worldwide.A series of potent neutralizing antibodies with defined epitopes targeting RBD have been recently identified with different strategies.However,being an RNA virus,the instability of the SARS-CoV-2 genome results in numerous S-protein variants with altered viral phenotypes.
