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Updated: May 15, 2026

Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
Published on: August 29, 2017
Most influenza a virions fail to express at least one essential viral protein
Christopher B Brooke1, William L Ince, Jens Wrammert
1Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
Abstract:
Segmentation of the influenza A virus (IAV) genome enables rapid gene reassortment at the cost of complicating the task of assembling the full viral genome. By simultaneously probing for the expression of multiple viral proteins in MDCK cells infected at a low multiplicity with IAV, we observe that the majority of infected cells lack detectable expression of one or more essential viral proteins. Consistent with this observation, up to 90% of IAV-infected cells fail to release infectious progeny, indicating that many IAV virions scored as noninfectious by traditional infectivity assays are capable of single-round infection. This fraction was not significantly affected by target or producer cell type but varied widely between different IAV strains. These data indicate that IAV exists primarily as a swarm of complementation-dependent semi-infectious virions, and thus traditional, propagation-dependent assays of infectivity may drastically misrepresent the true infectious potential of a virus population.
Insights
Influenza A virus (IAV) genome segmentation complicates assembly. Most infected cells lack essential proteins, producing semi-infectious virions that challenge traditional infectivity assays.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- The segmented genome of influenza A virus (IAV) facilitates rapid genetic reassortment.
- This segmentation presents challenges for complete viral genome assembly and understanding viral replication.
- Traditional infectivity assays rely on viral propagation, which may not accurately reflect virion potential.
Purpose of the Study:
- To investigate the expression of multiple viral proteins in IAV-infected cells.
- To determine the proportion of infected cells producing infectious progeny.
- To evaluate the accuracy of traditional infectivity assays for IAV.
Main Methods:
- Infection of Madin-Darby Canine Kidney (MDCK) cells with IAV at low multiplicity.
- Simultaneous probing for the expression of multiple viral proteins.
- Assessment of infectious progeny release and single-round infection capabilities.
Main Results:
- The majority of IAV-infected cells showed undetectable expression of one or more essential viral proteins.
- Up to 90% of IAV-infected cells failed to release infectious progeny.
- Many IAV virions, deemed noninfectious by traditional assays, were capable of single-round infection.
- The proportion of semi-infectious virions varied between IAV strains but was not significantly affected by cell type.
Conclusions:
- IAV predominantly exists as a swarm of complementation-dependent, semi-infectious virions.
- Traditional, propagation-dependent infectivity assays may significantly misrepresent the infectious potential of IAV populations.
- Understanding IAV replication requires considering the contribution of semi-infectious particles.
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