Tatsuya Sakai    Department   Kawasaki Medical School  Kawasaki Medical School, Department of Microbiology,    Position   Assistant Professor
Language	English
Title	Influenza A Virus Hemagglutinin and Neuraminidase Form a Novel Motile Machinery for Virus Invasion into Host Cells
Conference	The 63rd Annual Meeting of The Japanese Society for Virology
Promoters	Japanese Society for Virology
Conference Type	Nationwide Conferences
Presentation Type	Poster notice
Lecture Type	General
Publisher and common publisher	◎Tatsuya Sakai, Shin I. Nishimura, Tadasuke Naito, Mineki Saito
Date	2015/11/22
Venue (city and name of the country)	Fukuoka
Society abstract	The 63rd Annual Meeting of The Japanese Society for Virology. Program and Abstracts 220 2015
Summary	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.