Related Experiment Video

Updated: Aug 27, 2025

Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
07:55

Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies

Published on: August 29, 2017

11.8K

The evolutionary potential of influenza A virus hemagglutinin is highly constrained by epistatic interactions with

Tongyu Liu1, Yiquan Wang2, Timothy J C Tan3

  • 1Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Cell Host & Microbe
|September 23, 2022
PubMed

Antigenic evolution of the influenza A virus (IAV) hemagglutinin (HA) gene limits efforts to effectively control the spread of the virus in the population. Efforts to understand the mechanisms governing HA antigenic evolution typically examine the HA gene in isolation. This can ignore the importance of balancing HA receptor binding activities with the receptor-destroying activities of the viral neuraminidase (NA) to maintain viral fitness. We hypothesize that the need to maintain functional balance with NA significantly constrains the evolutionary potential of the HA. We use deep mutational scanning and show that variation in NA activity significantly reshapes the HA fitness landscape by modulating the overall mutational robustness of HA. Consistent with this, we observe that different NA backgrounds support the emergence of distinct repertoires of HA escape variants under neutralizing antibody pressure. Our results reveal a critical role for intersegment epistasis in influencing the evolutionary potential of the HA gene.

Keywords:
HA-NA balanceantigenic evolutionepistasisevolutionary constrainthemagglutinininfluenza virusmutational robustnessneuraminidase

More Related Videos

A Miniaturized Glycan Microarray Assay for Assessing Avidity and Specificity of Influenza A Virus Hemagglutinins10:32

A Miniaturized Glycan Microarray Assay for Assessing Avidity and Specificity of Influenza A Virus Hemagglutinins

Published on: May 29, 2016

8.0K
Fluorescence-based Neuraminidase Inhibition Assay to Assess the Susceptibility of Influenza Viruses to The Neuraminidase Inhibitor Class of Antivirals09:31

Fluorescence-based Neuraminidase Inhibition Assay to Assess the Susceptibility of Influenza Viruses to The Neuraminidase Inhibitor Class of Antivirals

Published on: April 15, 2017

18.4K

Related Concept Videos

Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
32.7K
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.2K
Viral Recombination00:57

Viral Recombination

Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
23.7K