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J Virol. 2013 Jan 30. [Epub ahead of print]
Reassortment Complements Spontaneous Mutation in Influenza A Virus NP and M1 genes to Accelerate Adaptation to a New Host.
Ince WL, Mbaye A, Bennink JR, Yewdell JW.
Source
Laboratory of Viral Diseases, National Institute of Allergies and Infectious Diseases, Bethesda, MD 20892.
Abstract
Influenza A virus (IAV) infects a remarkably wide variety of avian and mammalian hosts. Evolution finely hones IAV genes to optimally infect and transmit in a particular host species. Sporadically, IAV manages to jump between species, introducing novel antigenic strains into the new host population that wreak havoc until herd immunity develops. IAV adaptation to new hosts typically involves reassortment of IAV gene segments from co-infecting virus strains adapted to different hosts in conjunction with multiple adaptive mutations in the various IAV genes. To better understand host adaptation between mammalian species in real time, we passaged mouse-adapted A/PR8/34 (PR8) in guinea pigs. Guinea pigs, unlike mice, support spontaneous and robust IAV transmission. For some IAV strains, including PR8, adaptation is required for a virus to attain transmissibility, providing an opportunity to understand the evolution of transmissibility in guinea pigs. Multiple guinea pig-adapted PR8 mutants generated by serial nasal wash passaging in independent lines replicated more efficiently and transmitted by co-caging. All transmissible variants possessed one of two non-synonymous mutations in M1, either alone or in combination with mutations in PB2, HA, NP or NA. Rapid reassortment between independently selected variants combined beneficial mutations in NP and M1 to form the fittest transmitting virus. These findings provide further insight into genetic determinants in NP and M1 involved in PR8 IAV adaptation to transmit in a new host, and clearly show the benefit of a segmented genome in rapidly generating optimal combinations of mutations in IAV evolution.
PMID:
23365443
[PubMed - as supplied by publisher]
Reassortment Complements Spontaneous Mutation in Influenza A Virus NP and M1 genes to Accelerate Adaptation to a New Host.
Ince WL, Mbaye A, Bennink JR, Yewdell JW.
Source
Laboratory of Viral Diseases, National Institute of Allergies and Infectious Diseases, Bethesda, MD 20892.
Abstract
Influenza A virus (IAV) infects a remarkably wide variety of avian and mammalian hosts. Evolution finely hones IAV genes to optimally infect and transmit in a particular host species. Sporadically, IAV manages to jump between species, introducing novel antigenic strains into the new host population that wreak havoc until herd immunity develops. IAV adaptation to new hosts typically involves reassortment of IAV gene segments from co-infecting virus strains adapted to different hosts in conjunction with multiple adaptive mutations in the various IAV genes. To better understand host adaptation between mammalian species in real time, we passaged mouse-adapted A/PR8/34 (PR8) in guinea pigs. Guinea pigs, unlike mice, support spontaneous and robust IAV transmission. For some IAV strains, including PR8, adaptation is required for a virus to attain transmissibility, providing an opportunity to understand the evolution of transmissibility in guinea pigs. Multiple guinea pig-adapted PR8 mutants generated by serial nasal wash passaging in independent lines replicated more efficiently and transmitted by co-caging. All transmissible variants possessed one of two non-synonymous mutations in M1, either alone or in combination with mutations in PB2, HA, NP or NA. Rapid reassortment between independently selected variants combined beneficial mutations in NP and M1 to form the fittest transmitting virus. These findings provide further insight into genetic determinants in NP and M1 involved in PR8 IAV adaptation to transmit in a new host, and clearly show the benefit of a segmented genome in rapidly generating optimal combinations of mutations in IAV evolution.
PMID:
23365443
[PubMed - as supplied by publisher]
