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Virus Res. 2016 Sep 2. pii: S0168-1702(16)30248-9. doi: 10.1016/j.virusres.2016.09.002. [Epub ahead of print]
Mutations at highly conserved residues in influenza A(H1N1)pdm09 virus affect neuraminidase activity.
Romero-Beltran L1, Baker SF2, Puerto-Sol?s M1, Gonz?lez-Losa R1, Conde-Ferraez L1, Alvarez-S?nchez LC3, Mart?nez-Sobrido L2, Ayora-Talavera G4.
Author information
Abstract
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. Published by Elsevier B.V.
PMID: 27596738 DOI: 10.1016/j.virusres.2016.09.002
[PubMed - as supplied by publisher]
Mutations at highly conserved residues in influenza A(H1N1)pdm09 virus affect neuraminidase activity.
Romero-Beltran L1, Baker SF2, Puerto-Sol?s M1, Gonz?lez-Losa R1, Conde-Ferraez L1, Alvarez-S?nchez LC3, Mart?nez-Sobrido L2, Ayora-Talavera G4.
Author information
Abstract
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. Published by Elsevier B.V.
PMID: 27596738 DOI: 10.1016/j.virusres.2016.09.002
[PubMed - as supplied by publisher]