Changes in the Hemagglutinin and Internal Gene Segments Were Needed for Human Seasonal H3 Influenza A Virus to Efficiently Infect and Replicate in Swine

Author:

Rajao Daniela12ORCID,Abente Eugenio2,Powell Joshua2,Bolton Marcus2,Gauger Phillip3ORCID,Arruda Bailey2,Anderson Tavis2ORCID,Sutton Troy4ORCID,Perez Daniel1ORCID,Vincent Baker Amy2

Affiliation:

1. Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA

2. Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA 50010, USA

3. Department of Veterinary Diagnostic & Production Animal Medicine, Iowa State University, Ames, IA 50011, USA

4. Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA

Abstract

The current diversity of influenza A viruses (IAV) circulating in swine is largely a consequence of human-to-swine transmission events and consequent evolution in pigs. However, little is known about the requirements for human IAVs to transmit to and subsequently adapt in pigs. Novel human-like H3 viruses were detected in swine herds in the U.S. in 2012 and have continued to circulate and evolve in swine. We evaluated the contributions of gene segments on the ability of these viruses to infect pigs by using a series of in vitro models. For this purpose, reassortant viruses were generated by reverse genetics (rg) swapping the surface genes (hemagglutinin-HA and neuraminidase-NA) and internal gene segment backbones between a human-like H3N1 isolated from swine and a seasonal human H3N2 virus with common HA ancestry. Virus growth kinetics in porcine intestinal epithelial cells (SD-PJEC) and in ex-vivo porcine trachea explants were significantly reduced by replacing the swine-adapted HA with the human seasonal HA. Unlike the human HA, the swine-adapted HA demonstrated more abundant attachment to epithelial cells throughout the swine respiratory tract by virus histochemistry and increased entry into SD-PJEC swine cells. The human seasonal internal gene segments improved replication of the swine-adapted HA at 33 °C, but decreased replication at 40 °C. Although the HA was crucial for the infectivity in pigs and swine tissues, these results suggest that the adaptation of human seasonal H3 viruses to swine is multigenic and that the swine-adapted HA alone was not sufficient to confer the full phenotype of the wild-type swine-adapted virus.

Funder

The National Pork Board

the U.S. Department of Agriculture (USDA) Agricultural Research Service

Publisher

MDPI AG

Subject

Infectious Diseases,Microbiology (medical),General Immunology and Microbiology,Molecular Biology,Immunology and Allergy

Reference56 articles.

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