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Cell Rep. 2017 Sep 12;20(11):2538-2546. doi: 10.1016/j.celrep.2017.08.061.

Functional Insights into ANP32A-Dependent Influenza A Virus Polymerase Host Restriction.

Author information

1
Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
2
Institute of Medical Virology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Electronic address: hale.ben@virology.uzh.ch.

Abstract

Host restriction of influenza A virus limits pandemic emergence. The viral RNA polymerase (vPol) is an essential enzyme that must adapt for avian viruses to replicate in humans. Species differences in host ANP32A dictate adaptation: human ANP32A lacks an uncharacterized 33 amino-acid insertion that is present in avian ANP32A. Here, we uncover important contributions of host SUMOylation to vPol activity, including avANP32A function. We also identify a hydrophobic SUMO interaction motif (SIM)-like sequence unique to avANP32A that critically supports avian-signature vPol. Unrelated SIM sequences partially recapitulate this function when introduced into huANP32A. By investigating ANP32A-vPol interactions, we find that huANP32A interacts weakly with both human- and avian-signature vPols, while the hydrophobic motif of avANP32A promotes stronger interactions. Furthermore, we identify a highly acidic stretch in avANP32A that constitutes a major site of vPol interaction. Our data suggest compensatory mechanisms underlying vPol adaptation to host ANP32A independent of species-specific interactions.

KEYWORDS:

SUMO; host range; influenza virus; polymerase; restriction

PMID:
28903035
PMCID:
PMC5608968
DOI:
10.1016/j.celrep.2017.08.061
[Indexed for MEDLINE]
Free PMC Article

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