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Viruses. 2015 Dec 8;7(12):6458-75. doi: 10.3390/v7122950.

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.

Author information

1
Institute of Virology, Faculty of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany. st.siche@googlemail.com.
2
Institute of Virology, Faculty of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany. katharina.brett@gmail.com.
3
Robert Koch Institute, Advanced Light and Electron Microscopy (ZBS4), Nordufer 20, 13353 Berlin, Germany. moellerL@rki.de.
4
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia. kord@belozersky.msu.ru.
5
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia. ramil.mintaev@gmail.com.
6
I.I. Mechnikov Research Institute of Vaccines and Sera, Russian Academy of Medical Sciences, 105064 Moscow, Russia. ramil.mintaev@gmail.com.
7
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia. aba@belozersky.msu.ru.
8
Department of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia. aba@belozersky.msu.ru.
9
Institute of Virology, Faculty of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany. mveit@zedat.fu-berlin.de.

Abstract

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.

KEYWORDS:

J0101; M1; acylation; assembly; cytoplasmic tail; hemagglutinin; influenza virus; palmitoylation; transmembrane region

PMID:
26670246
PMCID:
PMC4690873
DOI:
10.3390/v7122950
[Indexed for MEDLINE]
Free PMC Article

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