Mutations in Influenza A Virus Neuraminidase and Hemagglutinin Confer Resistance against a Broadly Neutralizing Hemagglutinin Stem Antibody
Abstract
Influenza A virus is a public health threat for which currently available vaccines are not always effective. Broadly neutralizing antibodies that bind to the highly conserved stem region of the influenza virus hemagglutinin (HA) can neutralize many influenza virus strains. To understand how influenza virus can become resistant or escape such antibodies, we propagated influenza A virus in vitro with escalating concentrations of antibody and analyzed viral populations by whole-genome sequencing. We identified HA mutations near and distal to the antibody binding epitope that conferred resistance to antibody neutralization. Additionally, we identified a neuraminidase (NA) mutation that allowed the virus to grow in the presence of high concentrations of the antibody. Virus carrying dual mutations in HA and NA also grew under high antibody concentrations. We show that NA mutations mediate the escape of neutralization by antibodies against HA, highlighting the importance of a balance between HA and NA for optimal virus function.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 15, 2019
- Source ID
- 10.1128/jvi.01639-18
Entities
People
- Aneth S. Canale
- Celia A. Schiffer
- Daniel N. A. Bolon
- Jeffrey D. Jensen
- Jennifer P Wang
- Konstantin B. Zeldovich
- Kristina L. Prachanronarong
- Mohan Somasundaran
- Nese Kurt-yilmaz
- Nicholas Renzette
- Ping Liu
- Quan Zhu
- Robert W. Finberg
- Shurong Hou
- Thomas Han
- Timothy F. Kowalik
- Wayne A Marasco
- Yu-ping Poh
Organizations
- Arizona State University
- Harvard Medical School
- United States Department of Defense
- University of Massachusetts Medical School