Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Effect of Mice Adaptation Process on the Pathogenicity of Influenza A/South Africa/3626/2013 (H1N1)pdm09 Model Strain

Mohammad Al Farroukh
* ORCID logo ,
Irina Kiseleva
* ORCID logo ,
Ekaterina Stepanova
ORCID logo ,
Ekaterina Bazhenova
ORCID logo ,
Elena Krutikova
,
Artem Tkachev
,
Anna Chistyakova
ORCID logo ,
Andrey Rekstin
,
Ludmila Puchkova
ORCID logo ,
Larisa Rudenko
Version 1 : Received: 10 November 2023 / Approved: 13 November 2023 / Online: 13 November 2023 (14:17:10 CET)

A peer-reviewed article of this Preprint also exists.

Al Farroukh, M.; Kiseleva, I.; Stepanova, E.; Bazhenova, E.; Krutikova, E.; Tkachev, A.; Chistyakova, A.; Rekstin, A.; Puchkova, L.; Rudenko, L. The Effect of Mice Adaptation Process on the Pathogenicity of Influenza A/South Africa/3626/2013 (H1N1)pdm09 Model Strain. Int. J. Mol. Sci. 2023, 24, 17386. Al Farroukh, M.; Kiseleva, I.; Stepanova, E.; Bazhenova, E.; Krutikova, E.; Tkachev, A.; Chistyakova, A.; Rekstin, A.; Puchkova, L.; Rudenko, L. The Effect of Mice Adaptation Process on the Pathogenicity of Influenza A/South Africa/3626/2013 (H1N1)pdm09 Model Strain. Int. J. Mol. Sci. 2023, 24, 17386.

Abstract

Influenza virus strain A/South Africa/3626/2013 (H1N1)pdm09 (SA-WT) is a non-mouse-adapted model strain, which has naturally high pathogenic properties for mice. It has been suggested that the high pathogenicity of this strain for mice could be due to the three strain-specific substitutions in the polymerase complex (Q687R in PB1, N102T in PB2, and E358E/K heterogeneity also in PB2). To evaluate the role of these replacements, SA-WT was passaged five times in mouse lungs, and the genome of the mouse-adapted version of the SA-WT strain (SA-M5) was sequenced. SA-M5 lost E358E/K heterogeneity and retained E358, which is the prevalent amino acid at this position among H1N1pdm09 strains. Besides, in the hemagglutinin of SA-M5, two heterogeneous substitutions (G155G/E and S190S/R) were identified. Both viruses, SA-M5 and SA-WT, were compared for their toxicity, ability to replicate, pathogenicity, and immunogenicity for mice. In mice infected with SA-M5 or SA-WT strains, toxicity, virus titer in pulmonary homogenates, and mouse survival did not differ significantly. Contrarily, an increase in the immunogenicity of SA-M5 compared to SA-WT was observed. This increase could be due to the substitutions G155G/E and S190S/R in the HA of SA-M5. The prospects for using SA-M5 in studying the immunogenicity mechanisms were also discussed.

Keywords

Influenza A virus; A/South Africa/3626/2013 (H1N1)pdm09; H1N1pdm09 model strain; mutations in polymerase complex and hemagglutinin; pathogenicity; toxicity; immunogenicity

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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