Neuraminidase Receptor Binding Variants of Human Influenza A(H3N2) Viruses due to Substitution of Aspartic acid 151 in the Catalytic Site - Role in Vi

[tetano]

J Virol. 2010 Apr 21. [Epub ahead of print]
Neuraminidase Receptor Binding Variants of Human Influenza A(H3N2) Viruses due to Substitution of Aspartic acid 151 in the Catalytic Site - Role in Virus Attachment?

Lin YP, Gregory V, Collins P, Kloess J, Wharton S, Cattle N, Lackenby A, Daniels R, Hay A.

Virology Division, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA; Health Protection Agency, Centre for Infections, 61 Colindale Avenue, London NW9 5EQ.
Abstract

Changes in the receptor binding characteristics of human H3N2 viruses have been evident from changes in the agglutination of different red blood cells (RBCs) and reduced growth capacity of recent viruses, particularly in embryonated eggs. An additional peculiarity of viruses circulating in 2005-2009, has been the poor inhibition of haemagglutination, by post-infection ferret antisera, for many viruses isolated in MDCK cells, including homologous reference viruses. This was shown not to be due to antigenic change in the HA but to be the result of mutation in aspartic acid 151 of NA, to glycine, asparagine or alanine, which caused oseltamivir-sensitive agglutination of RBCs. The substitution D151G was shown to cause a change in the specificity of NA such that it acquired a capacity to bind receptors which were refractory to enzymatic cleavage, without altering its ability to remove receptors for HA. Thus, inhibition of NA-dependent agglutination by inclusion of oseltamivir carboxylate in the assay was effective in restoring the anti-HA specificity of the HI assay for monitoring antigenic change in the HA. Since the NA-dependent binding activity did not affect virus neutralization and virus populations in clinical specimens possessed at most low levels of '151 mutant', the biological significance of this feature of the NA, in for example immune evasion, is unclear. It is apparent, however, that an important role of aspartic acid 151 in the activity of NA may be to restrict the specificity of NA interaction and its receptor destroying activity to complement that of HA receptor binding.

PMID: 20410266 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/20410266?dopt=Abstract

 

[Giuseppe]

Re: Neuraminidase Receptor Binding Variants of Human Influenza A(H3N2) Viruses due to Substitution of Aspartic acid 151 in the Catalytic Site - Role in Virus Attachment?

[Source: US National Library of Medicine, (LINK). Edited.]

J Virol. 2010 Apr 21. [Epub ahead of print]

Neuraminidase Receptor Binding Variants of Human Influenza A(H3N2) Viruses due to Substitution of Aspartic acid 151 in the Catalytic Site - Role in Virus Attachment?

Lin YP, Gregory V, Collins P, Kloess J, Wharton S, Cattle N, Lackenby A, Daniels R, Hay A. - Virology Division, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA; Health Protection Agency, Centre for Infections, 61 Colindale Avenue, London NW9 5EQ.

Changes in the receptor binding characteristics of human H3N2 viruses have been evident from changes in the agglutination of different red blood cells (RBCs) and reduced growth capacity of recent viruses, particularly in embryonated eggs. An additional peculiarity of viruses circulating in 2005-2009, has been the poor inhibition of haemagglutination, by post-infection ferret antisera, for many viruses isolated in MDCK cells, including homologous reference viruses. This was shown not to be due to antigenic change in the HA but to be the result of mutation in aspartic acid 151 of NA, to glycine, asparagine or alanine, which caused oseltamivir-sensitive agglutination of RBCs. The substitution D151G was shown to cause a change in the specificity of NA such that it acquired a capacity to bind receptors which were refractory to enzymatic cleavage, without altering its ability to remove receptors for HA. Thus, inhibition of NA-dependent agglutination by inclusion of oseltamivir carboxylate in the assay was effective in restoring the anti-HA specificity of the HI assay for monitoring antigenic change in the HA. Since the NA-dependent binding activity did not affect virus neutralization and virus populations in clinical specimens possessed at most low levels of '151 mutant', the biological significance of this feature of the NA, in for example immune evasion, is unclear. It is apparent, however, that an important role of aspartic acid 151 in the activity of NA may be to restrict the specificity of NA interaction and its receptor destroying activity to complement that of HA receptor binding.

PMID: 20410266 [PubMed - as supplied by publisher]
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