Evaluating the Pandemic Potential of Influenza A Viruses in Primary Airway Models

Influenza A viruses (IAVs) are single stranded negative sense RNA viruses containing eight gene segments. IAVs have two genetic traits: (a) drift, resulting from mutations, usually in gene segments expressing the surface glycoproteins hemagglutinin and neuraminidase and (b) shift, re-assortment, which occurs when two viruses co-infect the same host and exchange gene segments. Migratory waterfowl are reservoirs of IAVs, while susceptible species include poultry, horses, humans, swine, and other mammals. Swine and avian IAVs are among the most important viral pathogens for animal health, causing outbreaks of respiratory disease in swine and poultry and occasional zoonotic transmission to humans. Swine are proposed as a “mixing” vessel since they are susceptible to avian and human influenza A viruses (IAVs) and the distribution of sialic acid receptors within their respiratory tract. H1N1 and H1N2 viruses have been circulating in pigs for over a century. The pre-dominate matrix gene has become the pdmM gene. The pdmM gene has been implicated as a determinate of respiratory transmission in hosts, which suggests that it might play an important role in the ability of viruses to be spread to humans. Experiments performed in this dissertation will evaluate the pandemic potential and tropism of swine and avian influenza as well as the effects of the matrix gene.