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Sci Rep. 2017 Aug 31;7(1):10205. doi: 10.1038/s41598-017-09560-z.

Prerequisites for the acquisition of mammalian pathogenicity by influenza A virus with a prototypic avian PB2 gene.

Author information

1
Laboratory of Avian Diseases, College of Veterinary Medicine, Seoul National University, 08826, Seoul, Republic of Korea.
2
Division of Antimicrobial Resistance, Center for Infectious Diseases, National Research Institute of Health, KCDC, Cheongju, Republic of Korea.
3
Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, 08826, Seoul, Republic of Korea.
4
Avian Disease Division, Animal and Plant Quarantine Agency, 177, Hyeoksin 8-ro, Gyeongsangbuk-do, 39660, Republic of Korea.
5
Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, 08826, Seoul, Republic of Korea.
6
Laboratory of Poultry Production Medicine, College of Veterinary Medicine, Seoul National University, 08826, Seoul, Republic of Korea. kwonhj01@snu.ac.kr.
7
Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, 08826, Seoul, Republic of Korea. kwonhj01@snu.ac.kr.
8
Farm Animal Clinical Training and Research Center (FACTRC), GBST, Seoul National University, Kangwon-do, Republic of Korea. kwonhj01@snu.ac.kr.

Abstract

The polymerase of avian influenza A virus (AIV) is a heterotrimer composed of PB2, PB1, and PA. PB2 plays a role in overcoming the host barrier; however, the genetic prerequisites for avian PB2 to acquire mammalian pathogenic mutations have not been well elucidated. Previously, we identified a prototypic avian PB2 that conferred non-replicative and non-pathogenic traits to a PR8-derived recombinant virus when it was used to infect mice. Here, we demonstrated that key amino acid mutations (I66M, I109V, and I133V, collectively referred to as MVV) of this prototypic avian PB2 increase the replication efficiency of recombinant PR8 virus carrying the mutated PB2 in both avian and mammalian hosts. The MVV mutations caused no weight loss in mice, but they did allow replication in infected lungs, and the viruses acquired fatal mammalian pathogenic mutations such as Q591R/K, E627K, or D701N in the infected lungs. The MVV mutations are located at the interfaces of the trimer and are predicted to increase the strength of this structure. Thus, gaining MVV mutations might be the first step for AIV to acquire mammalian pathogenicity. These results provide new insights into the evolution of AIV in birds and mammals.

PMID:
28860593
PMCID:
PMC5579056
DOI:
10.1038/s41598-017-09560-z
[Indexed for MEDLINE]
Free PMC Article

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