A complex epistatic network limits the mutational reversibility in the influenza hemagglutinin receptor-binding site.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29593268.
- Also identified by DOI 10.1038/s41467-018-03663-5 and PMC identifier 5871881.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The hemagglutinin (HA) receptor-binding site (RBS) in human influenza A viruses is critical for attachment to host cells, which imposes a functional constraint on its natural evolution. On the other hand, being part of the major antigenic sites, the HA RBS of human H3N2 viruses needs to constantly mutate to evade the immune system. From large-scale mutagenesis experiments, we here show that several of the natural RBS substitutions become integrated into an extensive epistatic network that prevents substitution reversion. X-ray structural analysis reveals the mechanistic consequences as well as changes in the mode of receptor binding. Further studies are necessary to elucidate whether such entrenchment limits future options for immune escape or adversely affect long-term viral fitness.
Medical subject headings
- Binding Sites
- Epistasis, Genetic
- Hemagglutinin Glycoproteins, Influenza Virus
- Influenza, Human
- Mutation
- Receptors, Virus