Mutations in PB2 and HA are crucial for the increased virulence and transmissibility of H1N1 swine influenza virus in mammalian models

Autor: Junyi Hu, Zhe Hu, Yandi Wei, Ming Zhang, Senlin Wang, Qi Tong, Honglei Sun, Juan Pu, Jinhua Liu, Yipeng Sun
Rok vydání: 2021
Předmět:
Zdroj: Veterinary microbiology. 265
ISSN: 1873-2542
Popis: Genetic analyses indicated that the pandemic H1N1/2009 influenza virus originated from a swine influenza virus (SIV). However, SIVs bearing the same constellation of genetic features as H1N1/2009 have not been isolated. Understanding the adaptation of SIVs with such genotypes in a new host may provide clues regarding the emergence of pandemic strains such as H1N1/2009. In this study, an artificial SIV with the H1N1/2009 genotype (rH1N1) was sequentially passaged in mice through two independent series, yielding multiple mouse-adapted mutants with high genetic diversity and increased virulence. These experiments were meant to mimic genetic bottlenecks during adaptation of wild viruses with rH1N1 genotypes in a new host. Molecular substitutions in the mouse-adapted variants mainly occurred in genes encoding surface proteins (hemagglutinin [HA] and neuraminidase [NA]) and polymerase proteins (polymerase basic 2 [PB2], polymerase basic 1 [PB1], polymerase acid [PA] proteins and nucleoprotein [NP]). The PB2
Databáze: OpenAIRE