RESUMO
Different subtypes of influenza A viruses (IAVs) cause different pathogenic phenotypes after infecting human bodies. Analysis of the interactions between viral proteins and the host proteins may provide insights into the pathogenic mechanisms of the virus. In this paper, we found that the same proteins (nucleoprotein and neuraminidase) of H1N1 and H5N1 have different impacts on the NF-κB activation. By further examining the virus-host protein-protein interactions, we found that both NP and NA proteins of the H1N1 and H5N1 viruses target different host proteins. These results indicate that different subtypes of influenza viruses target different human proteins and pathways leading to different pathogenic phenotypes.
Assuntos
Interações Hospedeiro-Patógeno/genética , Vírus da Influenza A Subtipo H1N1/genética , Virus da Influenza A Subtipo H5N1/genética , Influenza Humana/genética , Humanos , Vírus da Influenza A Subtipo H1N1/patogenicidade , Virus da Influenza A Subtipo H5N1/patogenicidade , Influenza Humana/virologia , NF-kappa B/genética , Neuraminidase/genética , Proteínas do Nucleocapsídeo , Nucleoproteínas/genética , Fenótipo , Mapas de Interação de Proteínas/genética , Proteínas Virais/genéticaRESUMO
Enterohemorrhagic E. coli (EHEC) is a highly pathogenic bacterial strain capable of inducing severe gastrointestinal disease. Here, we show that EHEC uses the T3SS effector NleF to counteract the host inflammatory response by dampening caspase-4-mediated inflammatory epithelial cell death and by preventing the production of IL-1ß. The other two inflammatory caspases, caspase-1 and caspase-5, are not involved in EHEC ΔnleF-induced inflammatory cell death. We found that NleF not only interrupted the heterodimerization of caspase-4-p19 and caspase-4-p10, but also inhibited the interaction of caspase-1 and caspase-4. The last four amino acids of the NleF carboxy terminus are essential in inhibiting caspase-4-dependent inflammatory cell death.
Assuntos
Caspases Iniciadoras/metabolismo , Escherichia coli Enteropatogênica/metabolismo , Células Epiteliais/metabolismo , Proteínas de Escherichia coli/metabolismo , Fatores de Virulência/metabolismo , Caspases Iniciadoras/genética , Linhagem Celular Tumoral , Escherichia coli Enteropatogênica/genética , Escherichia coli Enteropatogênica/patogenicidade , Células Epiteliais/patologia , Proteínas de Escherichia coli/genética , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/microbiologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Domínios Proteicos , Fatores de Virulência/genéticaRESUMO
A comprehensive study of cross-species transmission and inter-regional migration would provide insights into the global ecology of influenza A viruses (IAVs). To this end, we assembled 17,241 non-redundant IAV whole-genome sequences with complete epidemiological information. We hierarchically divided the movements of IAVs into the cross-species transmission in each region and the inter-regional migration driven by each host species. We then systematically identified the potential cross-species transmission and inter-regional migration events. Cross-species transmission networks were obtained for each gene segment of the IAVs. Waterfowl, domestic birds and swine showed higher degrees of connection than did other species in all of the transmission networks. East Asia and Southeast Asia were hot regions for avian-mammal transmissions. Swine and migratory birds were the dominant species for global virus delivery. The importance of swine was reemphasized because it has not only provided an environment for adaptive evolution during the avian-human transmission of IAVs (as incubators) but also served as a key species for the global dissemination of the viruses (as carriers). Therefore, monitoring the global live trade of swine and survey of migratory birds along flyways would be beneficial for the prevention and control of IAVs.
