Stability of the Influenza Virus Hemagglutinin Protein Correlates with Evolutionary Dynamics
Abstract
One of the constraints on fast-evolving viruses, such as influenza virus, is protein stability, or how strongly the folded protein holds together. Despite the importance of this protein property, there has been limited investigation of the impact of the stability of the influenza virus hemagglutinin protein—the primary antibody target of the immune system—on its evolution. Using a combination of computational estimates of stability and experiments, our analysis found that viruses with more-stable hemagglutinin proteins were associated with long-term persistence in the population. There are two potential reasons for the observed persistence. One is that more-stable proteins tolerate destabilizing mutations that less-stable proteins could not, thus increasing opportunities for immune escape. The second is that greater stability increases the fitness of the virus through increased production of infectious particles. Further research on the relative importance of these mechanisms could help inform the annual influenza vaccine composition decision process.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 28, 2018
- Source ID
- 10.1128/mspheredirect.00554-17
Entities
People
- Adrian Serohijos
- Andrew Feldman
- Andrew P. Lane
- Andrew Pekosz
- Brendan D. Smith
- Deena Blumenkrantz
- Eili Y. Klein
- Eugene I. Shakhnovich
- Jeong-Mo Choi
- João V. Rodrigues
Organizations
- Hartwell Foundation
- Harvard University
- Johns Hopkins School of Medicine
- Johns Hopkins University
- National Institute of Allergy and Infectious Diseases
- Université de Montréal