Influenza A virus: Interspecies transmission and mechanisms of replication and virulence.

摘要

Influenza A viruses are widespread in nature and infect many different species, including, humans, birds and pigs. There is ample evidence for the interspecies transmission of influenza viruses. In this regard, avian species provide an important reservoir for influenza viruses and pigs serve as the "mixing vessel" that produces avian-mammalian virus reassortants. The transmission of a swine virus to humans has been documented several times since 1975. We examined a recent zoonotic transmission of H1N1 swine influenza viruses and characterized six influenza viruses isolated from two people infected by exposure to experimentally infected pigs. In this study, we examined the antigenic and genetic characteristics of these human isolates. Extensive sequence analysis revealed that the H1N1 virus responsible was a direct descendent of the virus used to challenge the pigs. This study illustrates how easily swine H1N1 viruses cross species barriers and directly infect people.; We also used avian viruses to study questions regarding influenza replication, virulence and pathogenesis. We focused on the hemagglutinin (HA) RNA segment of a highly pathogenic H5N9 avian influenza virus, A/Ty/Ontario/7732/66 (Ty/Ont), which rapidly produces lymphoid depletion and death in poultry. The HA of this virus contains a putative second positive strand promoter sequence. We examined RNA isolated from infected cells and found a substantial amount of subgenomic HA (sHA) RNA, suggesting that this sequence serves as a promoter. Further analysis demonstrated that production of this sHA RNA mapped to the putative internal promoter and some of this sHA RNA was capped and polyadenylated. However, a protein was not produced by in vitro translation or eukaryotic expression. In addition, the levels of sHA produced in virulent and avirulent reassortants, as well as naturally occurring H5 isolates, indicate that other influenza viral proteins are important in the recognition of this putative internal promoter. Our findings may contribute to a better understanding of interspecies transmission, as well as the cis-acting signals involved in replication and, potentially, the virulence of influenza A viruses.