サカイ　タツヤ   Tatsuya Sakai   堺　立也    所属   川崎医科大学  医学部 基礎医学　微生物学    職種   講師
言語種別	英語
発表タイトル	Influenza A Virus Hemagglutinin and Neuraminidase Form a Novel Motile Machinery for Virus Invasion into Host Cells
会議名	The 63rd Annual Meeting of The Japanese Society for Virology
主催者	Japanese Society for Virology
学会区分	全国規模の学会
発表形式	ポスター掲示
講演区分	一般
発表者・共同発表者	◎Tatsuya Sakai, Shin I. Nishimura, Tadasuke Naito, Mineki Saito
発表年月日	2015/11/22
開催地 （都市, 国名）	Fukuoka
学会抄録	The 63rd Annual Meeting of The Japanese Society for Virology. Program and Abstracts 220 2015
概要	Influenza A virus (IAV) membrane proteins hemagglutinin (HA) and neuraminidase (NA) are determinants of virus infectivity, transmissibility, pathogenicity, host specificity and major antigenicity. HA binds to a viral receptor, a sialoglycoprotein or sialoglycolipid, on the host cell and mediates virus attachment to the cell surface. The hydrolytic enzyme NA cleaves sialic acid from viral receptors and facilitates the release of progeny virus from host cells. NA has been also indicated to be involved in virus infection. However, the specifics of this NA role in virus infection remain unclear. Here, we report a novel function of HA and NA as virus motile machinery for virus infection. Using total internal reflection fluorescence microscopy, we examined IAV behavior on glass surfaces immobilized with receptors that mimicked cell surfaces. We found that viruses moved laterally either in a gradually (rolling) or saltatory manner (sliding), and that both movements were dependent upon viral NA activity. NA inhibitors completely blocked both rolling and sliding. Further analysis of mutant viruses with reduced NA activity demonstrated that virus movements were dependent on not only enzymatic activity of NA but also expression level of NA protein. We also observed NA-dependent virus movements on the surface of erythrocytes. Limiting virus movements with a NA inhibitor resulted in a 25% decrease in virus internalization into cultured A549 cells. We conclude that HAs exchange binding partner receptors iteratively, generating virus movements on the cell surface, and this exchange is facilitated by NA. The virus coordinates HA and NA to move on a cell surface toward endocytosis regions, where the virus can invade the host cell. Because the functional balance between HA affinity and NA catalytic activity is important for virus infection of specific host cells, the virus motility regulated by HA and NA may be a determinant of infectivity and host specificity of IAV.