RT Journal Article
SR Electronic
T1 Antibody neutralization of an influenza virus that uses neuraminidase for receptor binding
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.08.084954
DO 10.1101/2020.05.08.084954
A1 Lauren E. Gentles
A1 Hongquan Wan
A1 Maryna C. Eichelberger
A1 Jesse D. Bloom
YR 2020
UL http://biorxiv.org/content/early/2020/05/09/2020.05.08.084954.abstract
AB Influenza virus infection elicits antibodies against the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Because HA is essential for viral entry, antibodies targeting HA often potently neutralize the virus in single-cycle infection assays. But antibodies against NA are not potently neutralizing in such assays, since NA is dispensable for single-cycle infection. Here we show that a modified influenza virus that depends on NA for receptor binding is much more sensitive than a virus with receptor-binding HA to neutralization by some anti-NA antibodies. Specifically, virus with a receptor-binding G147R N1 NA and a binding-deficient HA is completely neutralized in single-cycle infections by an antibody that binds near the NA active site. Infection is also substantially inhibited by antibodies that bind NA epitopes distant from the active site. Finally, we demonstrate that this modified virus can be used to efficiently select mutations in NA that escape antibody binding, a task that can be laborious with typical influenza viruses that are not well-neutralized by anti-NA antibodies. Thus, viruses dependent on NA for receptor binding allow for sensitive in vitro detection of antibodies binding near the catalytic site of NA and enable selection of viral escape mutants.Competing Interest StatementThe authors have declared no competing interest.