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

Publication date: 12 September 2017
Source:Cell Reports, Volume 20, Issue 11
Author(s): Patricia Domingues, Benjamin G. Hale
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.

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Teaser

Species differences in cellular ANP32A dictate influenza A virus polymerase host restriction. Domingues and Hale describe the contribution of host SUMOylation to viral polymerase activity and identify a SUMO interaction motif-like sequence unique to avian ANP32A that promotes interaction with the viral polymerase and is critical for determining host range.


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