tetano
Editor, Senior Moderator
Science 24 October 2014:
Vol. 346 no. 6208 pp. 473-477
DOI: 10.1126/science.1257037
Report
Influenza A virus uses the aggresome processing machinery for host cell entry
Indranil Banerjee1,*,?,
Yasuyuki Miyake2,
Samuel Philip Nobs3,
Christoph Schneider3,
Peter Horvath4,
Manfred Kopf3,
Patrick Matthias2,5,
Ari Helenius1,?,
Yohei Yamauchi1,?
+ Author Affiliations
1Institute of Biochemistry, Eidgenossische Technische Hochschule (ETH) Zurich, Switzerland.
2Epigenetics, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
3Institute of Molecular Health Sciences, ETH Zurich, Switzerland.
4Synthetic and Systems Biology Unit, Biological Research Center, Szeged, Hungary.
5Faculty of Sciences, University of Basel, Basel, Switzerland.
+ Author Notes
↵* Present address: Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland.
↵? Present address: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
↵?Corresponding author. E-mail: ari.helenius@bc.biol.ethz.ch (A.H.); yohei.yamauchi@bc.biol.ethz.ch (Y.Y.)
Abstract
Editor's Summary
During cell entry, capsids of incoming influenza A viruses (IAVs) must be uncoated before viral ribonucleoproteins (vRNPs) can enter the nucleus for replication. After hemagglutinin-mediated membrane fusion in late endocytic vacuoles, the vRNPs and the matrix proteins dissociate from each other and disperse within the cytosol. Here, we found that for capsid disassembly, IAV takes advantage of the host cell?s aggresome formation and disassembly machinery. The capsids mimicked misfolded protein aggregates by carrying unanchored ubiquitin chains that activated a histone deacetylase 6 (HDAC6)?dependent pathway. The ubiquitin-binding domain was essential for recruitment of HDAC6 to viral fusion sites and for efficient uncoating and infection. That other components of the aggresome processing machinery, including dynein, dynactin, and myosin II, were also required suggested that physical forces generated by microtubule- and actin-associated motors are essential for IAV entry.
http://www.sciencemag.org/content/346/6208/473.short
Vol. 346 no. 6208 pp. 473-477
DOI: 10.1126/science.1257037
Report
Influenza A virus uses the aggresome processing machinery for host cell entry
Indranil Banerjee1,*,?,
Yasuyuki Miyake2,
Samuel Philip Nobs3,
Christoph Schneider3,
Peter Horvath4,
Manfred Kopf3,
Patrick Matthias2,5,
Ari Helenius1,?,
Yohei Yamauchi1,?
+ Author Affiliations
1Institute of Biochemistry, Eidgenossische Technische Hochschule (ETH) Zurich, Switzerland.
2Epigenetics, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
3Institute of Molecular Health Sciences, ETH Zurich, Switzerland.
4Synthetic and Systems Biology Unit, Biological Research Center, Szeged, Hungary.
5Faculty of Sciences, University of Basel, Basel, Switzerland.
+ Author Notes
↵* Present address: Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland.
↵? Present address: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
↵?Corresponding author. E-mail: ari.helenius@bc.biol.ethz.ch (A.H.); yohei.yamauchi@bc.biol.ethz.ch (Y.Y.)
Abstract
Editor's Summary
During cell entry, capsids of incoming influenza A viruses (IAVs) must be uncoated before viral ribonucleoproteins (vRNPs) can enter the nucleus for replication. After hemagglutinin-mediated membrane fusion in late endocytic vacuoles, the vRNPs and the matrix proteins dissociate from each other and disperse within the cytosol. Here, we found that for capsid disassembly, IAV takes advantage of the host cell?s aggresome formation and disassembly machinery. The capsids mimicked misfolded protein aggregates by carrying unanchored ubiquitin chains that activated a histone deacetylase 6 (HDAC6)?dependent pathway. The ubiquitin-binding domain was essential for recruitment of HDAC6 to viral fusion sites and for efficient uncoating and infection. That other components of the aggresome processing machinery, including dynein, dynactin, and myosin II, were also required suggested that physical forces generated by microtubule- and actin-associated motors are essential for IAV entry.
http://www.sciencemag.org/content/346/6208/473.short