Tetherin sensitivity of influenza A viruses is strain specific: Role of hemagglutinin and neuraminidase

Gnirss K, Zmora P, Blazejewska P, Winkler M, et al. Tetherin sensitivity of influenza A viruses is strain specific: Role of hemagglutinin and neuraminidase. J Virol 2015 Jun 24. pii: JVI.00615
submited by kickingbird at Jul, 5, 2015 18:57 PM from J Virol 2015 Jun 24. pii: JVI.00615

The expression of the antiviral host cell factor tetherin is induced by interferon and can inhibit the release of enveloped viruses from infected cells. The Vpu protein of HIV-1 antagonizes the antiviral activity of tetherin and tetherin antagonists with Vpu-like activity have been identified in other viruses. In contrast, it is incompletely understood whether tetherin inhibits influenza A virus (FLUAV) release and whether FLUAV encodes tetherin antagonists. Here, we show that release of several laboratory-adapted and a seasonal FLUAV strain is inhibited by tetherin while pandemic FLUAV A/Hamburg/4/2009 is resistant. Studies with a virus-like particle system and analysis of reassortant viruses provided evidence that the viral hemagglutinin (HA) is an important determinant of tetherin antagonism but requires the presence of its cognate neuraminidase (NA) to inhibit tetherin. Finally, tetherin antagonism by FLUAV was dependent on the virion context, since retrovirus release from tetherin-positive cells was not rescued, and correlated with a HA, NA-dependent reduction in tetherin expression. In sum, our study identifies HA and NA proteins of certain pandemic FLUAV as tetherin antagonists, which has important implications for understanding FLUAV pathogenesis.