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Updated: Oct 20, 2025
Affinity Purification of Influenza Virus Ribonucleoprotein Complexes from the Chromatin of Infected Cells
Published on: June 3, 2012
A natural variant in ANP32B impairs influenza virus replication in human cells
Ecco Staller1,2, Carol M Sheppard1, Laury Baillon1
1Department of Infectious Disease, Faculty of Medicine, Imperial College London, UK.
Abstract:
Viruses require host factors to support their replication, and genetic variation in such factors can affect susceptibility to infectious disease. Influenza virus replication in human cells relies on ANP32 proteins, which are involved in assembly of replication-competent dimeric influenza virus polymerase (FluPol) complexes. Here, we investigate naturally occurring single nucleotide variants (SNV) in the human Anp32A and Anp32B genes. We note that variant rs182096718 in Anp32B is found at a higher frequency than other variants in either gene. This SNV results in a D130A substitution in ANP32B, which is less able to support FluPol activity than wild-type ANP32B and binds FluPol with lower affinity. Interestingly, ANP32B-D130A exerts a dominant negative effect over wild-type ANP32B and interferes with the functionally redundant paralogue ANP32A. FluPol activity and virus replication are attenuated in CRISPR-edited cells expressing wild-type ANP32A and mutant ANP32B-D130A. We propose a model in which the D130A mutation impairs FluPol dimer formation, thus resulting in compromised replication. We suggest that both homozygous and heterozygous carriers of rs182096718 may have some genetic protection against influenza viruses.
Insights
Genetic variants in human ANP32B may offer protection against influenza. A specific ANP32B variant (rs182096718) impairs influenza virus polymerase activity, potentially reducing susceptibility to infection.
Area of Science:
- Virology
- Genetics
- Immunology
Background:
- Viral replication depends on host factors, and genetic variations in these factors influence disease susceptibility.
- Influenza virus replication in human cells requires ANP32 proteins for the assembly of functional influenza virus polymerase (FluPol) complexes.
Purpose of the Study:
- To investigate naturally occurring single nucleotide variants (SNVs) in human ANP32A and ANP32B genes.
- To determine the impact of the rs182096718 SNV in ANP32B on influenza virus replication.
Main Methods:
- Analysis of SNVs in human ANP32A and ANP32B genes.
- Functional characterization of the ANP32B D130A substitution and its effect on FluPol activity.
- CRISPR-edited cell models to assess viral replication.
Main Results:
- The rs182096718 SNV in ANP32B, leading to a D130A substitution, reduces ANP32B's ability to support FluPol activity and lowers its binding affinity to FluPol.
- ANP32B-D130A exhibits a dominant-negative effect over wild-type ANP32B and interferes with ANP32A.
- CRISPR-edited cells expressing ANP32A and ANP32B-D130A showed attenuated FluPol activity and virus replication.
Conclusions:
- The D130A mutation in ANP32B impairs FluPol dimer formation, leading to compromised influenza virus replication.
- Homozygous and heterozygous carriers of the rs182096718 variant may possess genetic protection against influenza viruses.
