Pandemic Influenza A Viruses Escape from Restriction by Human MxA through Adaptive Mutations in the Nucleoprotein

PLoS Pathogens

Petra Zimmermann¹  Benjamin Mänz¹  Otto Haller¹  Georg Kochs¹  Veronika Götz¹  Dominik Dornfeld¹  Martin Schwemmle¹  Roland Zell² 

[1] Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany;Institute of Virology und Antiviral Therapy, Universitätsklinikum Jena, Friedrich Schiller University Jena, Jena, Germany

关键词: Influenza A virus;    H5N1;    Polymerases;    Antimicrobial resistance;    Microbial mutation;    Swine;    Plasmid construction;    H1N1;   

DOI  :  10.1371/journal.ppat.1003279

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The interferon-induced dynamin-like MxA GTPase restricts the replication of influenza A viruses. We identified adaptive mutations in the nucleoprotein (NP) of pandemic strains A/Brevig Mission/1/1918 (1918) and A/Hamburg/4/2009 (pH1N1) that confer MxA resistance. These resistance-associated amino acids in NP differ between the two strains but form a similar discrete surface-exposed cluster in the body domain of NP, indicating that MxA resistance evolved independently. The 1918 cluster was conserved in all descendent strains of seasonal influenza viruses. Introduction of this cluster into the NP of the MxA-sensitive influenza virus A/Thailand/1(KAN-1)/04 (H5N1) resulted in a gain of MxA resistance coupled with a decrease in viral replication fitness. Conversely, introduction of MxA-sensitive amino acids into pH1N1 NP enhanced viral growth in Mx-negative cells. We conclude that human MxA represents a barrier against zoonotic introduction of avian influenza viruses and that adaptive mutations in the viral NP should be carefully monitored.

【 授权许可】

CC BY