AbstractsMedical & Health Science

Studies on Interspecies and Intraspecies Transmission of Influenza A Viruses

by Hadi M. Yassine

Institution: The Ohio State University
Department: Veterinary Preventive Medicine
Degree: PhD
Year: 2009
Keywords: Virology; Influenza; H1N1; H3N2; Swine; Turkeys; Transmission
Record ID: 1860954
Full text PDF: http://rave.ohiolink.edu/etdc/view?acc_num=osu1243451078


Type A influenza is the only genus in the Orthomyxoviradae family that is highly infectious to variety of animal species, including human, pigs, wild and domestic birds, horses, cats, dogs, ferrets, seals, whales, and others. Avian viruses are generally thought to preferentially bind the N-acetylneuraminic acid-a2,3-galactose (NeuAca2,3Gal) form of sialic acid receptors and human viruses preferentially bind to NeuAca2,6Gal sialic acid receptors. Pigs express substantial amount of both forms of sialic acids on their upper respiratory epithelial cells, and it is believed that both avian and human influenza viruses can attach to the appropriate receptors and infect pigs. Hence, pigs have been postulated to serve as a “mixing vessels” in which two or more influenza viruses can co-infect and undergo reassortment with potential for development of new viruses that can transmit to and infect other species. An H1N1 influenza A virus, A/swine/Ohio/24366/07, was isolated from pigs in an Ohio County fair. Twenty-six people that came in contact with the infected pigs developed respiratory disease and two of these people were laboratory confirmed as H1N1 by the Centers for Disease Control and Prevention (CDC). Hence, we genetically and antigenically characterized three H1N1 swine influenza viruses isolated from Ohio in 2004, 2006, and 2007. All viruses were triple reassortants, with genes from human, swine, and avian lineage viruses. Although expressed antigenic similarity, viruses showed antigenic changes in their genetic makeup. All three viruses shared multiple amino acids at the receptor binding domain with human viruses, and two of which replicated significantly in human airway epithelial cells. Triple reassortant H3N2 influenza viruses emerged in swine in 1998 and then in turkeys in 2003. In 2004, we isolated triple reassortant H3N2 viruses from turkey breeder hens in Ohio and Illinois. The Illinois flock was vaccinated twice with an inactivated vaccine containing H1N1 and H3N2 viruses of swine origin before the outbreak. Using the the Archetti and Horsfall formula, three turkey viruses were shown to be genetically and antigenically similar to each other but were antigenically distantly similar to swine virus vaccine strain as well as duck and human viruses of the same subtype. Testing their interspecies transmission between swine and turkeys, we identified viruses (TR H3N2) with different transmission potential between both species. Some viruses were able to transmit both ways between the swine and turkeys, some transmitted only one way from swine to turkeys and some that did not transmit either way. Interestingly, changes were observed on the HA but not the NA protein upon transmission of A/turkey/Ohio/313053/04 virus between swine and turkeys. Using reverse genetics, we created single gene reassortants between two strains of potentially different transmission behavior, and tested their replication in pigs and turkeys. It was evident that the hemagglutinin gene plays a critical but not…