Adaptation of influenza A(H1N1)pdm09 virus in experimental mouse models

E A Prokopyeva; I A Sobolev; M V Prokopyev; A M Shestopalov

doi:10.1016/j.meegid.2016.01.022

Adaptation of influenza A(H1N1)pdm09 virus in experimental mouse models

Infect Genet Evol. 2016 Apr:39:265-271. doi: 10.1016/j.meegid.2016.01.022. Epub 2016 Jan 30.

Authors

E A Prokopyeva¹, I A Sobolev², M V Prokopyev³, A M Shestopalov²

Affiliations

¹ Novosibirsk State University, 630090 Novosibirsk, Russian Federation; Federal State Budgetary Scientific Institution "Research Institute of Experimental and Clinical Medicine", Siberian Branch of the Russian Academy of Medical Sciences, 630117 Novosibirsk, Russian Federation. Electronic address: ellap@bk.ru.
² Federal State Budgetary Scientific Institution "Research Institute of Experimental and Clinical Medicine", Siberian Branch of the Russian Academy of Medical Sciences, 630117 Novosibirsk, Russian Federation.
³ Novosibirsk State University, 630090 Novosibirsk, Russian Federation.

PMID: 26829383
DOI: 10.1016/j.meegid.2016.01.022

Abstract

In the present study, three mouse-adapted variants of influenza A(H1N1)pdm09 virus were obtained by lung-to-lung passages of BALB/c, C57BL/6z and CD1 mice. The significantly increased virulence and pathogenicity of all of the mouse-adapted variants induced 100% mortality in the adapted mice. Genetic analysis indicated that the increased virulence of all of the mouse-adapted variants reflected the incremental acquisition of several mutations in PB2, PB1, HA, NP, NA, and NS2 proteins. Identical amino acid substitutions were also detected in all of the mouse-adapted variants of A(H1N1)pdm09 virus, including PB2 (K251R), PB1 (V652A), NP (I353V), NA (I106V, N248D) and NS1 (G159E). Apparently, influenza A(H1N1)pdm09 virus easily adapted to the host after serial passages in the lungs, inducing 100% lethality in the last experimental group. However, cross-challenge revealed that not all adapted variants are pathogenic for different laboratory mice. Such important results should be considered when using the influenza mice model.

Keywords: BALB/c; C57BL/6z and CD1 mice; Influenza А(H1N1)pdm09 virus adaptation; Interstitial pneumonia; Lungs; Nonstructural protein PB1-F2; Protein mutation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptation, Biological*
Amino Acid Substitution
Animals
Cell Line
Computational Biology / methods
Disease Models, Animal
Genome, Viral
High-Throughput Nucleotide Sequencing
Influenza A Virus, H1N1 Subtype / physiology*
Lung / pathology
Lung / virology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mutation
Orthomyxoviridae Infections / mortality
Orthomyxoviridae Infections / virology*
Viral Load
Viral Proteins / genetics
Virulence / genetics

Substances

Viral Proteins