Due to their inability to generate a complete immune response, mice knockout for type I interferon （IFN） receptors （Ifnar-/-） are more susceptible to viral infections, and are thus commonly used for pathogenesis s...Due to their inability to generate a complete immune response, mice knockout for type I interferon （IFN） receptors （Ifnar-/-） are more susceptible to viral infections, and are thus commonly used for pathogenesis studies. This mouse model has been used to study many diseases caused by highly pathogenic viruses from many families, including the Flaviviridae, Filoviridae, Arenaviridae, Bunyaviridae, Henipaviridae, and Togaviridae. In this review, we summarize the findings from these animal studies, and discuss the pros and cons of using this model versus other known methods for studying pathogenesis in animals.展开更多
The membrane-proximal external region(MPER)of Lassa virus(LASV)glycoprotein complex(GPC)is critical in modulating its functionality.Till now,the high-resolution structure of the intact GPC,including MPER is not availa...The membrane-proximal external region(MPER)of Lassa virus(LASV)glycoprotein complex(GPC)is critical in modulating its functionality.Till now,the high-resolution structure of the intact GPC,including MPER is not available.In this study,we used alanine substitution to scan all 16 residues located in LASV MPER.Western blotting and quantification fusion assay showed that the residues located at the C terminus of the HR2(M414 and L415)and N terminus of the MPER(K417 and Y419)are critical for GPC-mediated membrane fusion function.Furthermore,cell surface biotinylation experiments revealed that M414 A,K417 A and Y419 A expressed similar levels as WT,whereas L415 A mutant led to a reduction of mature GPC on the cell surface.Moreover,substitution of these residues with the similar residue such as M414 L,L415 I,K417 R and Y419 F would partly compensate the loss of the fusion activity caused by the alanine mutant in these sites.Results from this study showed that several key residues in the MPER region are indispensable to promote the conformational changes that drive fusion events and shed light on the structure analysis of LASV GPC and anti-LASV therapeutics.展开更多
Arenaviruses belong to the family of RNA viruses that can infect humans in various ways and cause different degrees of mortality.Rodents is the mainly hosts.Human pathogenic arenaviruses include lymphocytic choroid me...Arenaviruses belong to the family of RNA viruses that can infect humans in various ways and cause different degrees of mortality.Rodents is the mainly hosts.Human pathogenic arenaviruses include lymphocytic choroid meningitis,Lassa virus group and Takarib virus group,which cause human lymphocytic choriomeningitis and human hemorrhagic diseases.Rodents account for about 43%of mammalian species.At present,more than 30 highly pathogenic viruses have been found in rodents,including arenaviruses.The arenaviridae that infects rodents are mainly mammalian arenaviruses.This article reviews the etiology,clinicopathology,epidemiology,prevention and control of arenavirus,and provides references for the research and prevention of arenavirus.展开更多
Exploration and activity are often described as trade-offs between the fitness benefits of gathering information and resources, and the potential costs of increasing exposure to predators and para- sites. More explora...Exploration and activity are often described as trade-offs between the fitness benefits of gathering information and resources, and the potential costs of increasing exposure to predators and para- sites. More exploratory individuals are predicted to have higher rates of parasitism, but this relationship has rarely been examined for virus infections in wild populations. Here, we used the multimammate mouse Mastomys natalensis to investigate the relationship between exploration, activity, and infection with Morogoro virus （MORV）. We characterized individual exploratory behav- ior （open field and novel object tests） and activity （trap diversity）, and quantified the relationship between these traits and infection status using linear regression. We found that M. natalensis expresses consistent individual differences, or personality types, in exploratory behavior （repeat- ability of 0.30, 95% CI： 0.21-0.36）. In addition, we found a significant contrasting effect of age on ex- ploration and activity where juveniles display higher exploration levels than adults, but lower field- activity. There was however no statistical evidence for a behavioral syndrome between these 2 traits. Contrary to our expectations, we found no correlation between MORV infection status and exploratory behavior or activity, which suggests that these behaviors may not increase exposure probability to MORV infection. This would further imply that variation in viral infection between individuals is not affected by between-individual variation in exploration and activity.展开更多
基金supported by the National Natural Science Foundation of China International Cooperation and Exchange Program(8161101193)the National Science and Technology Major Project(2016ZX10004222)to G.Wong
文摘Due to their inability to generate a complete immune response, mice knockout for type I interferon （IFN） receptors （Ifnar-/-） are more susceptible to viral infections, and are thus commonly used for pathogenesis studies. This mouse model has been used to study many diseases caused by highly pathogenic viruses from many families, including the Flaviviridae, Filoviridae, Arenaviridae, Bunyaviridae, Henipaviridae, and Togaviridae. In this review, we summarize the findings from these animal studies, and discuss the pros and cons of using this model versus other known methods for studying pathogenesis in animals.
基金the National Key Research and Development Program of China (2018YFA0507204)the National Natural Sciences Foundation of China (31670165)+1 种基金Wuhan National Biosafety Laboratory,Chinese Academy of Sciences Advanced Customer Cultivation Project (2019ACCP-MS03)the Open Research Fund Program of the State Key Laboratory of Virology of China (2018IOV001)。
文摘The membrane-proximal external region(MPER)of Lassa virus(LASV)glycoprotein complex(GPC)is critical in modulating its functionality.Till now,the high-resolution structure of the intact GPC,including MPER is not available.In this study,we used alanine substitution to scan all 16 residues located in LASV MPER.Western blotting and quantification fusion assay showed that the residues located at the C terminus of the HR2(M414 and L415)and N terminus of the MPER(K417 and Y419)are critical for GPC-mediated membrane fusion function.Furthermore,cell surface biotinylation experiments revealed that M414 A,K417 A and Y419 A expressed similar levels as WT,whereas L415 A mutant led to a reduction of mature GPC on the cell surface.Moreover,substitution of these residues with the similar residue such as M414 L,L415 I,K417 R and Y419 F would partly compensate the loss of the fusion activity caused by the alanine mutant in these sites.Results from this study showed that several key residues in the MPER region are indispensable to promote the conformational changes that drive fusion events and shed light on the structure analysis of LASV GPC and anti-LASV therapeutics.
基金Hainan Provincial Higher Education Science Research Project(Hnky 2020‑33)Key Research and Development Plan of Hainan Province(ZDYF2020150)+4 种基金Major Science and Technology Project of Hainan Province(ZDKJ202003)National Natural Science Foundation of China(32060015)High level Talent Program of Hainan Natural Science Foundation(2019RC218)Hainan Academician Innovation Platform Project(YSPTZX202004)Hainan Academician Workstation Project(SRC200003)。
文摘Arenaviruses belong to the family of RNA viruses that can infect humans in various ways and cause different degrees of mortality.Rodents is the mainly hosts.Human pathogenic arenaviruses include lymphocytic choroid meningitis,Lassa virus group and Takarib virus group,which cause human lymphocytic choriomeningitis and human hemorrhagic diseases.Rodents account for about 43%of mammalian species.At present,more than 30 highly pathogenic viruses have been found in rodents,including arenaviruses.The arenaviridae that infects rodents are mainly mammalian arenaviruses.This article reviews the etiology,clinicopathology,epidemiology,prevention and control of arenavirus,and provides references for the research and prevention of arenavirus.
文摘Exploration and activity are often described as trade-offs between the fitness benefits of gathering information and resources, and the potential costs of increasing exposure to predators and para- sites. More exploratory individuals are predicted to have higher rates of parasitism, but this relationship has rarely been examined for virus infections in wild populations. Here, we used the multimammate mouse Mastomys natalensis to investigate the relationship between exploration, activity, and infection with Morogoro virus （MORV）. We characterized individual exploratory behav- ior （open field and novel object tests） and activity （trap diversity）, and quantified the relationship between these traits and infection status using linear regression. We found that M. natalensis expresses consistent individual differences, or personality types, in exploratory behavior （repeat- ability of 0.30, 95% CI： 0.21-0.36）. In addition, we found a significant contrasting effect of age on ex- ploration and activity where juveniles display higher exploration levels than adults, but lower field- activity. There was however no statistical evidence for a behavioral syndrome between these 2 traits. Contrary to our expectations, we found no correlation between MORV infection status and exploratory behavior or activity, which suggests that these behaviors may not increase exposure probability to MORV infection. This would further imply that variation in viral infection between individuals is not affected by between-individual variation in exploration and activity.
基金The Science and Technology Support Projects of China(Grant No.2007BAD87B11)the Science and Technology Research Projects,Hunan Province,Grant No.06NK3049)
