African swine fever virus(ASFV)infection poses enormous threats and challenges to the global pig industry;however,no effective vaccine is available against ASFV,attributing to the huge viral genome(approximately189 kb...African swine fever virus(ASFV)infection poses enormous threats and challenges to the global pig industry;however,no effective vaccine is available against ASFV,attributing to the huge viral genome(approximately189 kb)and numerous encoding products(>150 genes)due to the limited understanding on the molecular mechanisms of viral pathogenesis.Elucidating the host-factor/viral-protein interaction network will reveal new targets for developing novel antiviral therapies.Using proteomic analysis,we identified 255 cellular proteins that interact with the ASFV-encoded pE301R protein when transiently expressed in HEK293T cells.Gene ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)database enrichment,and protein-protein interaction(PPI)network analyses revealed that pE301R-interacting host proteins are potentially involved in various biological processes,including protein translation and folding,response to stimulation,and mitochondrial transmembrane transport.The interactions of two putative cellular proteins(apoptosis inducing factor mitochondria associated 1(AIFM1)and vimentin(VIM))with pE301R-apoptosis inducing factor have been verified by co-immunoprecipitation.Our study revealed the inhibitory role of pE301R in interferon(IFN)induction that involves VIM sequestration by pE301R,identified interactions between ASFV pE301R and cellular proteins,and predicted the potential function of pE301R and its associated biological processes,providing valuable information to enhance our understanding of viral protein function,pathogenesis,and potential candidates for the prevention and control of ASFV infection.展开更多
基金supported by the National Key R&D Program of China (2019YFA0905700,2018YFA0900400)Natural Science Foundation of China (31900147,32170038,32270088,M-0348 and 32161133013)+2 种基金the 111 Project (B16030)a Sino-German Helmholtz International Lab grantsupported by US National Institutes of Health grant 1R01CA251698-01 and CPRIT grants RP180349 and RP190077.
文摘African swine fever virus(ASFV)infection poses enormous threats and challenges to the global pig industry;however,no effective vaccine is available against ASFV,attributing to the huge viral genome(approximately189 kb)and numerous encoding products(>150 genes)due to the limited understanding on the molecular mechanisms of viral pathogenesis.Elucidating the host-factor/viral-protein interaction network will reveal new targets for developing novel antiviral therapies.Using proteomic analysis,we identified 255 cellular proteins that interact with the ASFV-encoded pE301R protein when transiently expressed in HEK293T cells.Gene ontology(GO)annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)database enrichment,and protein-protein interaction(PPI)network analyses revealed that pE301R-interacting host proteins are potentially involved in various biological processes,including protein translation and folding,response to stimulation,and mitochondrial transmembrane transport.The interactions of two putative cellular proteins(apoptosis inducing factor mitochondria associated 1(AIFM1)and vimentin(VIM))with pE301R-apoptosis inducing factor have been verified by co-immunoprecipitation.Our study revealed the inhibitory role of pE301R in interferon(IFN)induction that involves VIM sequestration by pE301R,identified interactions between ASFV pE301R and cellular proteins,and predicted the potential function of pE301R and its associated biological processes,providing valuable information to enhance our understanding of viral protein function,pathogenesis,and potential candidates for the prevention and control of ASFV infection.
