skip to main content

SciTech ConnectSciTech Connect

Title: Pleiotropic effects of hemagglutinin amino acid substitutions of H5 influenza escape mutants

In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We examined pH optimum of fusion, temperatures of HA heat inactivation, and in vitro and in vivo replication kinetics of the previously obtained influenza H5 escape mutants. Our results showed that HA1 N142K mutation significantly lowered the pH of fusion optimum. Mutations of the escape mutants located in the HA lateral loop significantly affected H5 HA thermostability (P<0.05). HA changes at positions 131, 144, 145, and 156 and substitutions at positions 131, 142, 145, and 156 affected the replicative ability of H5 escape mutants in vitro and in vivo, respectively. Overall, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. We believe that the monitoring of pleiotropic effects of the HA mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential. - Highlights: • HA1 N142K mutation significantly lowered the pH of fusion optimum. • Mutations located in the HA lateral loop significantly affected H5 HA thermostability. • HA changes at positions 131, 142, 144, 145, and 156 affected the replicative ability of H5 mutants. • Acquisition of glycosylation site could lead to the emergence of multiple pleiotropicmore » effects.« less
Authors:
; ; ; ;  [1] ;  [2] ;  [1]
  1. D.I. Ivanovsky Institute of Virology, 123098 Moscow (Russian Federation)
  2. FDA CDER, 29 Lincoln Drive, Bethesda, MD 20892 (United States)
Publication Date:
OSTI Identifier:
22436666
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 447; Journal Issue: 1-2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMINO ACIDS; ANTIBODIES; HEAT; HYDROGEN 5; IN VITRO; IN VIVO; INACTIVATION; INFLUENZA; MONITORING; MUTANTS; MUTATIONS; PH VALUE; SPECIFICITY