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Gnirß, K.* ; Zmora, P.* ; Blazejewska, P.* ; Winkler, M.* ; Lins, A.* ; Nehlmeier, I.* ; Gärtner, S.* ; Moldenhauer, A.S.* ; Hofmann-Winkler, H.* ; Wolff, T.* ; Schindler, M. ; Pöhlmann, S.*

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

J. Virol. 89, 9178-9188 (2015)
Verlagsversion Postprint DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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. IMPORTANCE: Influenza A virus (FLUAV) infection is responsible for substantial global morbidity and mortality and understanding how the virus evades immune defenses of the host may uncover novel targets for antiviral intervention. Tetherin is an antiviral effector molecule of the innate immune system which can contribute to control of viral invasion. However, it has been unclear whether FLUAV are inhibited by tetherin and whether these viruses encode tetherin antagonizing proteins. Our observation that several pandemic FLUAV can counteract tetherin via their HA and NA proteins identifies these proteins as novel tetherin antagonists and indicates that HA/NA-dependent inactivation of innate defenses may contribute to the efficient spread of pandemic FLUAV.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0022-538X
e-ISSN 1098-5514
Zeitschrift Journal of Virology
Quellenangaben Band: 89, Heft: 18, Seiten: 9178-9188 Artikelnummer: , Supplement: ,
Verlag American Society for Microbiology (ASM)
Begutachtungsstatus Peer reviewed