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

Influenza A viruses (IAV) are still a cause of concern for public health and veterinary services worldwide. With (−) RNA-segmented genome architecture, influenza viruses are prone to reassortment and can generate a great variety of strains, some capable of crossing interspecies barriers. Seasonal IAV strains continuously spread from humans to pigs, leading to multiple reassortation events with strains endemic to swine. Due to its high adaptability to humans, a reassortant strain based on “human-like” genes could potentially be a carrier of avian origin segments responsible for high virulence, and hence become the next pandemic strain with unseen pathogenicity. The rapid evolution of sequencing methods has provided a fast and cost-efficient way to assess the genetic diversity of IAV. In this study, we investigated the genetic diversity of swine influenza viruses (swIAVs) collected from Polish farms. A total of 376 samples were collected from 11 farms. The infection was confirmed in 112 cases. The isolates were subjected to next-generation sequencing (NGS), resulting in 93 full genome sequences. Phylogenetic analysis classified 59 isolates as genotype T (H1avN2g) and 34 isolates as genotype P (H1pdmN1pdm), all of which had an internal gene cassette (IGC) derived from the H1N1pdm09-like strain. These data are consistent with evolutionary trends in European swIAVs. The applied methodology proved to be useful in monitoring the genetic diversity of IAV at the human–animal interface.

Section: Discussionmentioning

confidence: 99%

“…The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/v15091893/s1 [63], Table S1: Reference strains dataset and accession numbers.…”

Section: Supplementary Materialsmentioning

confidence: 99%

Genetic Diversity of Type A Influenza Viruses Found in Swine Herds in Northwestern Poland from 2017 to 2019: The One Health Perspective

Rabalski,

Kosinski,

Cybulski

et al. 2023

“…A total of 10 initial passages were chosen based on previous studies in which mouse-adapted strains of IBV [23] as well as various IAV subtypes were deemed sufficient to increase lethality of the viruses [39,40]. This was also performed more recently for swine influenza H1 viruses [41]. Since 10 passages is often fewer than is required to mouse-adapt IBV [24][25][26], this served as our benchmark for potential improvement on established methods from the literature.…”

Section: Discussionmentioning

confidence: 99%

Expanding Mouse-Adapted Yamagata-like Influenza B Viruses in Eggs Enhances In Vivo Lethality in BALB/c Mice

Pekarek

Petro-Turnquist

Rubrum

et al. 2022

Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouse-adapting IBV can produce highly pathogenic viruses through serial lung passaging in mice. Previous studies have highlighted amino acid changes throughout the viral genome correlating with increased pathogenicity, but no consensus mutations have been determined. We aimed to show that growth system can play a role in mouse-adapted IBV lethality. Two Yamagata-lineage IBVs were serially passaged 10 times in mouse lungs before expansion in embryonated eggs or Madin–Darby canine kidney cells (London line) for use in challenge studies. We observed that virus grown in embryonated eggs was significantly more lethal in mice than the same virus grown in cell culture. Ten additional serial lung passages of one strain again showed virus grown in eggs was more lethal than virus grown in cells. Additionally, no mutations in the surface glycoprotein amino acid sequences correlated to differences in lethality. Our results suggest growth system can influence lethality of mouse-adapted IBVs after serial lung passaging. Further research can highlight improved mechanisms for developing animal disease models for IBV vaccine research.

“…Once viruses enter the respiratory tract of the recipient host, they replicate efficiently and multiply rapidly, affecting transmissibility and increasing the potential for airborne transmission. Researchers also investigated the impact and corresponding mechanism of polymerase mutation sites on mammalian transmission models [ 160 , 162 , 166 ]. When replicating within ferrets, recombinant H7N9 viruses with the PB2 E627K and E701N mutations exhibit increased viral polymerase activity and are effectively spread through respiratory droplets [ 167 ].…”

Section: Molecular Markers and Mechanisms Of Influenza A Virus Cross-...mentioning

confidence: 99%

Molecular Markers and Mechanisms of Influenza A Virus Cross-Species Transmission and New Host Adaptation

Guo,

Zhou,

Yan

et al. 2024

Influenza A viruses continue to be a serious health risk to people and result in a large-scale socio-economic loss. Avian influenza viruses typically do not replicate efficiently in mammals, but through the accumulation of mutations or genetic reassortment, they can overcome interspecies barriers, adapt to new hosts, and spread among them. Zoonotic influenza A viruses sporadically infect humans and exhibit limited human-to-human transmission. However, further adaptation of these viruses to humans may result in airborne transmissible viruses with pandemic potential. Therefore, we are beginning to understand genetic changes and mechanisms that may influence interspecific adaptation, cross-species transmission, and the pandemic potential of influenza A viruses. We also discuss the genetic and phenotypic traits associated with the airborne transmission of influenza A viruses in order to provide theoretical guidance for the surveillance of new strains with pandemic potential and the prevention of pandemics.