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A unique feature of swine ANP32A provides susceptibility to avian influenza virus infection in pigs.
- Source :
-
PLoS pathogens [PLoS Pathog] 2020 Feb 21; Vol. 16 (2), pp. e1008330. Date of Electronic Publication: 2020 Feb 21 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Both the replication and transcription of the influenza virus are catalyzed by the viral polymerase complex. The polymerases of most avian influenza A viruses have poor performance in mammalian cells, which is considered to be one of the important species barriers. Pigs have been long considered as important intermediate hosts for interspecies transmission of the avian influenza virus, because of their susceptibility to infection with both avian and mammalian influenza viruses. However, the molecular basis of influenza polymerase adaptation in pigs remains largely unknown. ANP32A and ANP32B proteins have been identified as playing fundamental roles in influenza virus replication and host range determination. In this study, we found that swine ANP32A (swANP32A), unlike swine ANP32B or other mammalian ANP32A or B, shows stronger supporting activity to avian viral polymerase. Knockout of ANP32A in pig cells PK15 dramatically reduced avian influenza polymerase activity and viral infectivity, suggesting a unique feature of swANP32A in supporting avian influenza viral polymerase. This species-specific activity is mapped to two key sites, 106V and 156S, in swANP32A. Interestingly, the amino acid 106V is unique to pigs among all the vertebrate species studied, and when combined with 156S, exhibits positive epistasis in pigs. Mutation of 106V and 156S to the signature found in ANP32As from other mammalian species weakened the interaction between swANP32A and chicken viral polymerase, and reduced polymerase activity. Understanding the molecular basis of ANP32 proteins may help to discover new antiviral targets and design avian influenza resistant genome edited pigs.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Chickens
Host Specificity genetics
Host Specificity immunology
Humans
Influenza A Virus, H1N1 Subtype genetics
Influenza A Virus, H7N9 Subtype genetics
Influenza A virus metabolism
Influenza in Birds genetics
Influenza, Human virology
Intracellular Signaling Peptides and Proteins metabolism
Nuclear Proteins genetics
Nuclear Proteins metabolism
Orthomyxoviridae Infections
RNA-Binding Proteins genetics
RNA-Binding Proteins metabolism
RNA-Dependent RNA Polymerase metabolism
Swine genetics
Swine metabolism
Viral Proteins metabolism
Virus Replication
Influenza A virus genetics
Influenza, Human genetics
Swine virology
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 16
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 32084248
- Full Text :
- https://doi.org/10.1371/journal.ppat.1008330