Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Substitution Arg140Gly in HA/H7 Reduced the Virulence Highly Pathogenic Avian Influenza Virus H7N1

Version 1 : Received: 11 June 2021 / Approved: 15 June 2021 / Online: 15 June 2021 (14:29:26 CEST)

How to cite: Treshchalina, A.; Postnikova, Y.; Boravleva, E.; Gambaryan, A.; Belyakova, A.; Ishmukhametov, A.; Sadykova, G.; Prilipov, A.; Lomakina, N. Substitution Arg140Gly in HA/H7 Reduced the Virulence Highly Pathogenic Avian Influenza Virus H7N1. Preprints 2021, 2021060410 (doi: 10.20944/preprints202106.0410.v1). Treshchalina, A.; Postnikova, Y.; Boravleva, E.; Gambaryan, A.; Belyakova, A.; Ishmukhametov, A.; Sadykova, G.; Prilipov, A.; Lomakina, N. Substitution Arg140Gly in HA/H7 Reduced the Virulence Highly Pathogenic Avian Influenza Virus H7N1. Preprints 2021, 2021060410 (doi: 10.20944/preprints202106.0410.v1).

Abstract

The H7 subtype of avian influenza viruses (AIV) stands out among other AIV. The H7 viruses cir-culate in ducks, poultry, equine and have repeatedly caused outbreaks of disease in humans. In or-der to study the pathogenicity factors of H7N1 viruses, several variants were obtained, starting with laboratory strain, with a history of 12 passages through chicken embryos. This strain, A/chicken/Rostock/R0p/1934(H7N1) (R0p) had only 3 substitution in HA relatively A/Chicken/Rostock/45/34(H7N1), substitution Arg140Gly among them. 10 variants of this strain was obtained and studied to ascertain its biological property, genome stability and factors of patho-genicity. Strain R0p had decreased virulence for chicken, comparing with described in literature virulence of A/FPV Rostock/34 and A/chicken/Rostock/34 viruses. After 10 passages through the chicken lungs variant was obtained much more pathogenic than the starting R0p. The study of in-termediate passages through the chicken lungs showed that the jump in pathogenicity had occurred sharply between the fifth and sixth passage. By cloning these variants, a pair of strains (R5p and R6p) were obtained, and the complete genomes of these strains were sequenced. Single amino acid substitution was revealed, namely reversion Gly140Arg in HA1. This amino acid is located at the head part of the hemagglutinin, adjacent to the receptor-binding site. In addition to the increased pathogenicity for chicken and mice, R6p differs from R5p in the pattern of foci in cell culture and an increased affinity for a negatively charged receptor analogue, while maintaining a pattern of recep-tor binding specificity and the pH optimum of the HA conformational change.

Subject Areas

highly pathogenic avian influenza viruses, pathogenicity factors.

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