tetano
Editor, Senior Moderator
J Virol. 2013 Oct 9. [Epub ahead of print]
Evolution of the hemagglutinin protein of new pandemic H1N1 virus: Maintaining optimal receptor binding by compensatory substitutions.
de Vries RP, de Vries E, Mart?nez-Romero C, McBride R, van Kuppeveld F, Rottier PJ, Garc?a-Sastre A, Paulson JC, de Haan CA.
Source
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Abstract
Pandemic influenza A H1N1 virus (pH1N1) emerged in 2009. In the subsequent four years, it acquired several genetic changes in its hemagglutinin (HA). Mutations may be expected while adapting to the human host or upon evasion from adaptive immune responses. However, pH1N1 does not display any major antigenic changes so far. We examined the effect of the amino acid substitutions most frequently occurring in the pH1N1 HA protein before 04-01-2012, on the receptor-binding properties of the virus by using recombinant soluble HA trimers. Two changes (S186P and S188T) were shown to increase receptor-binding avidity of HA whereas two others (A137T and A200T) decreased binding avidity. Construction of an HA protein tree revealed the worldwide emergence of several HA variants during the last seasons. Strikingly, two major variants harbor combinations of substitutions (S186P/A137T and S188T/A200T, respectively) with opposite individual effects on binding. Stepwise reconstruction of the HA proteins of these variants demonstrated that the mutations that increase receptor-binding avidity are compensated by the acquisition of subsequent mutations. The combination of these substitutions restored the receptor-binding properties (avidity and specificity) of these HA variants to that of the parental virus. The results strongly suggest that the HA of pH1N1 was already optimally adapted to the human host upon its emergence in April 2009. Moreover, these results are in agreement with a recent model for antigenic drift, in which high and low receptor-binding avidity influenza A virus mutants alternate.
PMID:
24109242
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24109242
Evolution of the hemagglutinin protein of new pandemic H1N1 virus: Maintaining optimal receptor binding by compensatory substitutions.
de Vries RP, de Vries E, Mart?nez-Romero C, McBride R, van Kuppeveld F, Rottier PJ, Garc?a-Sastre A, Paulson JC, de Haan CA.
Source
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Abstract
Pandemic influenza A H1N1 virus (pH1N1) emerged in 2009. In the subsequent four years, it acquired several genetic changes in its hemagglutinin (HA). Mutations may be expected while adapting to the human host or upon evasion from adaptive immune responses. However, pH1N1 does not display any major antigenic changes so far. We examined the effect of the amino acid substitutions most frequently occurring in the pH1N1 HA protein before 04-01-2012, on the receptor-binding properties of the virus by using recombinant soluble HA trimers. Two changes (S186P and S188T) were shown to increase receptor-binding avidity of HA whereas two others (A137T and A200T) decreased binding avidity. Construction of an HA protein tree revealed the worldwide emergence of several HA variants during the last seasons. Strikingly, two major variants harbor combinations of substitutions (S186P/A137T and S188T/A200T, respectively) with opposite individual effects on binding. Stepwise reconstruction of the HA proteins of these variants demonstrated that the mutations that increase receptor-binding avidity are compensated by the acquisition of subsequent mutations. The combination of these substitutions restored the receptor-binding properties (avidity and specificity) of these HA variants to that of the parental virus. The results strongly suggest that the HA of pH1N1 was already optimally adapted to the human host upon its emergence in April 2009. Moreover, these results are in agreement with a recent model for antigenic drift, in which high and low receptor-binding avidity influenza A virus mutants alternate.
PMID:
24109242
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24109242