Mutations at highly conserved residues in influenza A(H1N1)pdm09 virus affect neuraminidase activity.

Autor: Romero-Beltran L; Laboratorio de Virología, Universidad Autonoma de Yucatan, Mexico., Baker SF; Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA., Puerto-Solís M; Laboratorio de Virología, Universidad Autonoma de Yucatan, Mexico., González-Losa R; Laboratorio de Virología, Universidad Autonoma de Yucatan, Mexico., Conde-Ferraez L; Laboratorio de Virología, Universidad Autonoma de Yucatan, Mexico., Alvarez-Sánchez LC; Laboratorio de Virología, Universidad Autonoma de Yucatan, Mexico; Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA., Martínez-Sobrido L; Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA., Ayora-Talavera G; Laboratorio de Virología, Universidad Autonoma de Yucatan, Mexico. Electronic address: talavera@correo.uady.mx.
Jazyk: angličtina
Zdroj: Virus research [Virus Res] 2016 Oct 02; Vol. 225, pp. 1-9. Date of Electronic Publication: 2016 Sep 03.
DOI: 10.1016/j.virusres.2016.09.002
Abstrakt: Influenza virus neuraminidase (NA) plays a pivotal role during viral growth since its sialidase activity allows the efficient release of nascent virions from infected cells. Consequently, mutations in the NA catalytic site affecting sialic acid (SA) cleavage may influence the biological properties of influenza viruses. This study reports two amino acid substitutions (N386K and P431S) in the NA of the influenza A(H1N1)pdm09 virus that emerged in 2009 in Mexico. The NA sialidase activity to cleave SA-like substrates, and viral growth were examined and the mutant viruses had various deficiencies. NA mutations N386K and P431S together or separately, and in the presence or absence of H275Y were further evaluated using recombinant influenza A/California/04/2009 (pH1N1) viruses containing single, double, or triple mutations. Viral growth was reduced in the presence of mutation P431S alone or combined with N386K and/or H275Y. Substrates hydrolysis was reduced when recombinant pH1N1 viruses were analyzed by NA inhibitory assays. Moreover, elution assays with guinea pig red blood cells indicated an unbalanced hemagglutinin (HA):NA functionality. Altogether, our data underline the functional significance of mutations at highly conserved sites in influenza virus NA glycoprotein and the occurrence of permissive mutations to compensate virus viability in vitro.
(Copyright © 2016 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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