Related Experiment Video

Updated: Jan 4, 2026

A Miniaturized Glycan Microarray Assay for Assessing Avidity and Specificity of Influenza A Virus Hemagglutinins
10:32

A Miniaturized Glycan Microarray Assay for Assessing Avidity and Specificity of Influenza A Virus Hemagglutinins

Published on: May 29, 2016

8.3K

Changes in the Receptor-Binding Properties of H3N2 Viruses during Long-Term Circulation in Humans

A S Gambaryan1, A Balish2, A I Klimov2

  • 1Chumakov Federal Scientific Center for Research and Development of Immune and Biological Products, Russian Academy of Sciences, Moscow, 108819, Russia. al.gambaryan@gmail.com.

Biochemistry. Biokhimiia
|November 8, 2019
PubMed

Insights

Influenza viruses H1N1 and H3N2 evolved to preferentially bind N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac) derivatives, with N-acetylneuraminic acid (Neu5Ac) being the optimal human receptor.

Area of Science:

  • Virology
  • Molecular Biology
  • Evolutionary Biology

Background:

  • Hemagglutinin (HA) residues Thr155, Glu158, and Ser228 are known to be critical for Neu5Gc recognition.
  • Previous studies indicated H1N1 and H3N2 influenza viruses exhibit distinct receptor binding preferences.
  • The non-adaptive nature of Neu5Gc binding is suggested by its sporadic occurrence and absence in human glycoconjugates.

Purpose of the Study:

  • To investigate the amino acid determinants of Neu5Gc-terminated receptor binding in influenza viruses.
  • To analyze the evolution of receptor specificity in H3N2 viruses concerning sialosides 6'SL and 6'SLN.
  • To determine the optimal natural human receptor for H1N1 and H3N2 influenza viruses.

Main Methods:

  • Analysis of hemagglutinin (HA) amino acid sequences from historical influenza virus isolates (1972-2003).
  • Correlation of specific HA amino acid substitutions (e.g., Lys145, Glu190Asp, Gly225Asp) with receptor binding phenotypes.
  • Examination of changes in sialoside binding affinity over time for H3N2 viruses.

Main Results:

  • Influenza viruses from 1972-1999 with Lysine at position 145 (Lys145) in HA bind Neu5Gc receptors, while those with Asparagine (Asn145) do not.
  • H3N2 viruses post-1993 acquired the ability to distinguish between 6'SL and 6'SLN, with increasing affinity for 6'SLN from 1992-2003.
  • Post-2003 H3N2 viruses lost binding to some sialosides but retained high affinity for 6'SLN, associated with new glycosylation sites and HA substitutions (Glu190Asp, Gly225Asp).

Conclusions:

  • Amino acid 145 in hemagglutinin is a key determinant for Neu5Gc receptor binding.
  • Convergent evolution in receptor specificity between H1N1 and H3N2 viruses suggests adaptation to a common human receptor.
  • N-acetylneuraminic acid (Neu5Ac) linked to N-acetylglucosamine (6'SLN) is identified as the optimal natural human receptor for these influenza virus strains.

More Related Videos

Monitoring Influenza Virus Survival Outside the Host Using Real-Time Cell Analysis09:02

Monitoring Influenza Virus Survival Outside the Host Using Real-Time Cell Analysis

Published on: February 20, 2021

3.4K
Measuring Influenza Neutralizing Antibody Responses to AH3N2 Viruses in Human Sera by Microneutralization Assays Using MDCK-SIAT1 Cells12:09

Measuring Influenza Neutralizing Antibody Responses to AH3N2 Viruses in Human Sera by Microneutralization Assays Using MDCK-SIAT1 Cells

Published on: November 22, 2017

18.6K

Related Concept Videos

Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
39.5K
Viral Recombination00:57

Viral Recombination

Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
24.8K