tetano
Editor, Senior Moderator
J Virol. 2013 Jul 3. [Epub ahead of print]
Single Hemagglutinin Mutations that Alter Both Antigenicity and Receptor Binding Avidity Influence Influenza Virus Antigenic Clustering.
Li Y, Bostick DL, Sullivan CB, Myers JL, Griesemer SB, St George K, Plotkin JB, Hensley SE.
Source
Wistar Vaccine Center, Wistar Institute, Philadelphia, PA 19104, USA.
Abstract
The hemagglutination-inhibition (HAI) assay is the primary measurement used for identifying antigenically novel influenza strains. HAI assays measure the amount of reference sera required to prevent virus binding to red blood cells. Receptor binding avidities of viral strains are not usually taken into account when interpreting these assays. Here, we created antigenic maps of human H3N2 viruses that computationally account for variation in viral receptor binding avidities. These new antigenic maps differ qualitatively from conventional antigenic maps based on HAI measurements alone. We experimentally focused on an antigenic cluster associated with a single N145K hemagglutinin (HA) substitution that occurred between 1992 and 1995. Reverse-genetics experiments demonstrated that the N145K HA mutation increases viral receptor binding avidity. ELISA analysis revealed that the N145K HA mutation does not prevent antibody binding; rather, viruses possessing this mutation escape anti-sera in HAI assays simply by attaching to cells more efficiently. Unexpectedly, we found an asymmetric antigenic effect of the N145K HA mutation. Once H3N2 viruses acquired K145, an epitope involving amino acid 145 became antigenically dominant. Anti-sera raised against an H3N2 strain possessing K145 had reduced reactivity to H3N2 strains possessing N145. Thus, individual mutations in HA can influence antigenic groupings of strains by altering receptor binding avidity and by changing the dominance of antibody responses. Our results indicate that it will be important to account for variation in viral receptor binding avidity when performing antigenic analyses, in order to identify genuine antigenic differences among influenza variants.
PMID:
23824816
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23824816
Single Hemagglutinin Mutations that Alter Both Antigenicity and Receptor Binding Avidity Influence Influenza Virus Antigenic Clustering.
Li Y, Bostick DL, Sullivan CB, Myers JL, Griesemer SB, St George K, Plotkin JB, Hensley SE.
Source
Wistar Vaccine Center, Wistar Institute, Philadelphia, PA 19104, USA.
Abstract
The hemagglutination-inhibition (HAI) assay is the primary measurement used for identifying antigenically novel influenza strains. HAI assays measure the amount of reference sera required to prevent virus binding to red blood cells. Receptor binding avidities of viral strains are not usually taken into account when interpreting these assays. Here, we created antigenic maps of human H3N2 viruses that computationally account for variation in viral receptor binding avidities. These new antigenic maps differ qualitatively from conventional antigenic maps based on HAI measurements alone. We experimentally focused on an antigenic cluster associated with a single N145K hemagglutinin (HA) substitution that occurred between 1992 and 1995. Reverse-genetics experiments demonstrated that the N145K HA mutation increases viral receptor binding avidity. ELISA analysis revealed that the N145K HA mutation does not prevent antibody binding; rather, viruses possessing this mutation escape anti-sera in HAI assays simply by attaching to cells more efficiently. Unexpectedly, we found an asymmetric antigenic effect of the N145K HA mutation. Once H3N2 viruses acquired K145, an epitope involving amino acid 145 became antigenically dominant. Anti-sera raised against an H3N2 strain possessing K145 had reduced reactivity to H3N2 strains possessing N145. Thus, individual mutations in HA can influence antigenic groupings of strains by altering receptor binding avidity and by changing the dominance of antibody responses. Our results indicate that it will be important to account for variation in viral receptor binding avidity when performing antigenic analyses, in order to identify genuine antigenic differences among influenza variants.
PMID:
23824816
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23824816