A perspective on the structural and functional constraints for immune evasion: insights from the influenza virus
By Nicholas C. Wu, Ian A. Wilson. 2017
170 citations recorded by the source corpus.
Influenza virus evolves rapidly to constantly escape from natural immunity. Most humoral immune responses to influenza virus target the hemagglutinin glycoprotein (HA), which is the major antigen on the surface of the virus. The HA is comprised of a globular head domain for receptor binding and a stem domain for membrane fusion. The major antigenic sites of HA are located in the globular head subdomain, which is highly tolerant of amino-acid substitutions and continual addition of glycosylation sites. Nonetheless, the evolution of the receptor-binding site (RBS) and the stem region on HA is severely constrained by their functional roles in engaging the host receptor and in mediating membrane fusion, respectively. Here, we review how broadly neutralizing antibodies (bnAbs) exploit these evolutionary constraints to protect against diverse influenza strains. We also discuss the emerging role of other epitopes that are conserved only in subsets of viruses. This rapidly increasing knowledge of the evolutionary biology, immunology, structural biology, and virology of influenza virus is invaluable for development and design of more universal influenza vaccines as well as novel therapeutics.
Subfields: Epidemiology, Radiology, Nuclear Medicine and Imaging
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Citations in the corpus
- Next-Generation Influenza Vaccines. (2020, background): “Although the head domain contains extremely neutralization-sensitive epitopes, these epitopes are under strong immune pressure and readily acquire mutations that evade antibody recognition without compromising receptor-binding properties (Wu and Wilson 2017).”