Submitted to: International Union of Microbiological Societies Proceedings/Abstracts
Publication Type: Abstract only
Publication Acceptance Date: 6/1/2005
Publication Date: 7/23/2005
Citation: Lekcharoensuk, P., Vincent, A.L., Lager, K.M., Solorzano, A., Garcia-Sastre, A., Richt, J.A. 2005. Establishment of a pig model for the 1930 H1N1 swine influenza virus and application of reverse genetics [abstract]. International Congress of Virology. p. 42. Interpretive Summary:
Technical Abstract: The aims of this study were to establish a pig model for the 1930 H1N1 swine influenza virus and its rescue by reverse genetics. Influenza A/swine/IA/15/30 H1N1 (ATCC VR333) is the first influenza virus isolated from swine and genetically related to the 1918 Spanish Flu virus. We inoculated thirty 4-week-old pigs with the H1N1 SIV. Pigs were euthanized at 3, 5 and 7 dpi. Average macroscopic lung lesion scores were 9%, 13% and 11% on 3, 5, and 7 dpi, respectively. Virus titers in the bronchioalveolar lavage were 10**4, 10**3.8 and 10**1.1 TCID50/ml at 3, 5 and 7 dpi, respectively. Virus shedding in nasal secretions at dpi 3 and 5 were significantly higher than those at 7 dpi. In vitro interferon beta bioassay showed that the 1930 SIV was able to inhibit type I interferon production, similar to other pathogenic influenza viruses. The sequence from the pig-passaged virus was compared to the ATCC VR333 GenBank reference sequence: HA, NA and NS genes were identical, PB2 had 99.9% homology with 2 nucleotide mutations, PA had 99.9% homology with one mutation resulting in a serine to cysteine substitution; one silent mutation was found in the NP and M genes. No PB1 reference sequence was found for comparison. We are now constructing an infectious clone using reverse genetics. In summary, we have established a pig model for studies on the pathogenicity of the 1930 H1N1 SIV and we are now constructing an infectious clone using reverse genetics. Since pigs are susceptible to swine, avian and human influenza viruses, a pig model in combination with the reverse genetics system could be a valuable tool for studying the molecular basis of virulence and genetic reassortment.