Evolutionarily conserved residues at an oligomerization interface of the influenza A virus neuraminidase are essential for viral survival

Abstract Neuraminidase (NA) is a homotetramer viral surface glycoprotein that is essential for virus release during influenza virus infections. Previous studies have not explored why influenza NA forms a tetramer when the bacterial monomer NA already exhibits excellent NA enzymatic activity levels....

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Published in:Virology (New York, N.Y.) N.Y.), 2013-12, Vol.447 (1), p.32-44
Main Authors: Mok, Chee-Keng, Chen, Guang-Wu, Shih, Kuei-Chung, Gong, Yu-Nong, Lin, Sue-Jane, Horng, Jim-Tong, Hsu, John T.-A, Chen, Chi-Jene, Shih, Shin-Ru
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Conserved residues
Conserved Sequence
DNA Mutational Analysis
Humans
Infectious Disease
Influenza A virus
Influenza A virus - genetics
Influenza A virus - physiology
Microbial Viability
Models, Molecular
Molecular Sequence Data
Neuraminidase (NA)
Neuraminidase (NA) enzymatic activity
Neuraminidase - chemistry
Neuraminidase - genetics
Neuraminidase - metabolism
Oligomerization
Protein Conformation
Protein Multimerization
Reverse Genetics
Sequence Alignment
Viral Plaque Assay
Viral Proteins - chemistry
Viral Proteins - genetics
Viral Proteins - metabolism
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Summary:Abstract Neuraminidase (NA) is a homotetramer viral surface glycoprotein that is essential for virus release during influenza virus infections. Previous studies have not explored why influenza NA forms a tetramer when the bacterial monomer NA already exhibits excellent NA enzymatic activity levels. In this study, we focused on 28 highly conserved residues among all NA subtypes, identifying 21 of 28 positions as crucial residues for viral survival by using reverse genetics. Maintaining NA enzymatic activity levels is critical and numerous conserved residues were located at the oligomerization interface; however, these mutations did not affect NA enzymatic activity levels or NA cellular localization, but rather affected the stability of NA oligomerization, suggesting that the oligomerization of NA is essential for viral viability. An increased understanding of the biological functions of NA, in particular NA oligomerization, could facilitate an alternative design for antivirals to combat influenza virus infections.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2013.08.012