Two Cytoplasmic Acylation Sites and an Adjacent Hydrophobic Residue, but No Other Conserved Amino Acids in the Cytoplasmic Tail of HA from Influenza A Virus Are Crucial for Virus Replication

Viruses

Stefanie Siche³  Katharina Brett³  Lars Möller²  Larisa V. Kordyukova¹  Ramil R. Mintaev¹  Andrei V. Alexeevski¹  Michael Veit³ 

[1] A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia;Robert Koch Institute, Advanced Light and Electron Microscopy (ZBS4), Nordufer 20, 13353 Berlin, Germany;Institute of Virology, Faculty of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany;

关键词: influenza virus;    assembly;    hemagglutinin;    cytoplasmic tail;    transmembrane region;    acylation;    palmitoylation;    M1;   

DOI  :  10.3390/v7122950

来源: mdpi

【 摘 要 】

Recruitment of the matrix protein M1 to the assembly site of the influenza virus is thought to be mediated by interactions with the cytoplasmic tail of hemagglutinin (HA). Based on a comprehensive sequence comparison of all sequences present in the database, we analyzed the effect of mutating conserved residues in the cytosol-facing part of the transmembrane region and cytoplasmic tail of HA (A/WSN/33 (H1N1) strain) on virus replication and morphology of virions. Removal of the two cytoplasmic acylation sites and substitution of a neighboring isoleucine by glutamine prevented rescue of infectious virions. In contrast, a conservative exchange of the same isoleucine, non-conservative exchanges of glycine and glutamine, deletion of the acylation site at the end of the transmembrane region and shifting it into the tail did not affect virus morphology and had only subtle effects on virus growth and on the incorporation of M1 and Ribo-Nucleoprotein Particles (RNPs). Thus, assuming that essential amino acids are conserved between HA subtypes we suggest that, besides the two cytoplasmic acylation sites (including adjacent hydrophobic residues), no other amino acids in the cytoplasmic tail of HA are indispensable for virus assembly and budding.

【 授权许可】

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