Influenza A virus hemagglutinin and neuraminidase act as novel motile machinery

Tatsuya Sakai,Shin I Nishimura,Mineki Saito,Tadasuke Naito

doi:10.1038/srep45043

Abstract

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 virus 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 accelerates the release of progeny virus from host cells. In this study, we identified a novel function of HA and NA as machinery for viral motility. HAs exchanged binding partner receptors iteratively, generating virus movement on a receptor-coated glass surface instead of a cell surface. The virus movement was also dependent on NA. Virus movement mediated by HA and NA resulted in a three to four-fold increase in virus internalisation by cultured cells. We concluded that cooperation of HA and NA moves IAV particles on a cell surface and enhances virus infection of host cells.

Highlights

Influenza virus, Semliki Forest virus (SFV), and vesicular stomatitis virus (VSV) are enveloped viruses that are internalised into host cells by cellular endocytosis[1]
To investigate whether Influenza A virus (IAV) movement occurs via the exchange of HA-receptor binding pairs, we coated the surfaces of glass coverslips with fetuin as a viral receptor and investigated the movement of the IAV strain Aichi/2/68(H3N2) (Aichi2) conjugated to a fluorescent probe, octadecyl rhodamine B (R18) on the fetuin-coated surfaces using total internal reflection fluorescence microscopy (TIRFM) combined with single particle tracking analyses (Fig. 1b)
Virus gliding was observed at a very low concentration of virus, indicating that gliding is different from one virus being released from the surface and another virus immediately attaching to the surface

Summary

Introduction

Semliki Forest virus (SFV), and vesicular stomatitis virus (VSV) are enveloped viruses that are internalised into host cells by cellular endocytosis[1]. Murine leukaemia virus and VSV attach to cellular protrusions and rapidly move to the root of the protrusion by actin- and myosin-driving mechanisms, which is mediated by the viral receptor[10] Both mechanisms of virus movement employ lateral movements of the viral receptor in the membrane lipid bilayer, which are essentially identical to the endocytosis of transferrin, low density lipoprotein (LDL), insulin, and epidermal growth factor (EGF) (Fig. 1a, left). Compared with these physiological ligands and other related viruses, binding of influenza virus HA to its receptor is remarkably weak. These data demonstrated a novel role of HA and NA in virus motility and entry

Methods

Results

Conclusion