| Author |
Lorusso, Alessio Ciacci-Zanella, Janice R. Zanella, Eraldo L. Pena, Lindomar Perez, Daniel R. Lager, Kelly M. Rajão, Daniela S. Loving, Crystal L. Kitikoon, Pravina Vincent, Amy L. |
| Description |
Country affiliation: United States Author Affiliation: Lorusso A ( Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA.); Ciacci-Zanella JR ( Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA Laboratório de Virologia, Embrapa Suínos e Aves, Concórdia, Santa Catarina, Brazil.); Zanella EL ( Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA Universidade de Passo Fundo, Brazil.); Pena L ( Department of Veterinary Medicine, University of Maryland, College Park, MD, USA Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD, USA.); Perez DR ( Department of Veterinary Medicine, University of Maryland, College Park, MD, USA Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD, USA.); Lager KM ( Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA.); Rajão DS ( Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA.); Loving CL ( Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA.); Kitikoon P ( Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA.); Vincent AL ( Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA amy.vincent@ars.usda.gov.) |
| Abstract |
Interactions between the viral surface glycoprotein haemagglutinin (HA) and the corresponding receptors on host cells is one important aspect of influenza virus infection. Mutations in HA have been described to affect pathogenicity, antigenicity and the transmission of influenza viruses. Here, we detected polymorphisms present in HA genes of two pandemic 2009 H1N1 (H1N1pdm09) isolates, A/California/04/2009 (Ca/09) and A/Mexico/4108/2009 (Mx/09), that resulted in amino acid changes at positions 186 (S to P) and 194 (L to I) of the mature HA1 protein. Although not reported in the published H1N1pdm09 consensus sequence, the P186 genotype was more readily detected in primary infected and contact-naïve pigs when inoculated with a heterogeneous mixed stock of Ca/09. Using reverse genetics, we engineered Ca/09 and Mx/09 genomes by introducing Ca/09 HA with two naturally occurring variants expressing S186/I194 (HA-S/I) and P186/L194 (HA-P/L), respectively. The Ca/09 HA with the combination of P186/L194 with either the Ca/09 or Mx/09 backbone resulted in higher and prolonged viral shedding in naïve pigs. This efficiency appeared to be more likely through an advantage in cell surface attachment rather than replication efficiency. Although these mutations occurred within the receptor-binding pocket and the Sb antigenic site, they did not affect serological cross-reactivity. Relative increases of P186 in publicly available sequences from swine H1N1pdm09 viruses supported the experimental data, indicating this amino acid substitution conferred an advantage in swine. |
| Subject Keyword |
Research Support, U.s. Gov't, Non-p.h.s. Discipline Virology Transmission Swine Diseases Influenza A Virus, H1n1 Subtype Virus Shedding Metabolism Hemagglutinin Glycoproteins, Influenza Virus Journal Article Research Support, U.s. Gov't, P.h.s. Virology Polymorphism, Genetic Animals Gene Expression Regulation, Viral Swine Nose Genetics Physiology Orthomyxoviridae Infections Veterinary |
