A time course study of Influenza A and Streptococcus pyogenes secondary super- infections in a mouse model.
Date of Award
Dr. Victor Huber
Dr. Lisa Moore
Dr. David Swanson
super-infection, Influenza, Streptococcus
Bacterial Infections and Mycoses
Historically, influenza A infections in humans have been complicated by secondary infections with bacteria such as Streptococcus pneumonia, Staphylococcus aureus, and Streptococcus pyogenes. Super-infections occur when a primary infection, usually viral, allows for a second infection to take hold in the host. These secondary infections are usually bacterial. While death associated with primary influenza infections remains a serious healthcare concern, these super-infections are largely responsible for the mortality associated with influenza. Streptococcus pyogenes or group A Streptococcus super-infections in particular were responsible for 27% of the deaths in the 1918 Spanish flu (H1N1) pandemic and more recently have been estimated to have caused up to 29% of the deaths associated with bacterial co-infection during the 2009 H1N1 flu pandemic. Previous work has determined that different strains of influenza A viruses result in differing severities of secondary bacterial super-infections. Our hypothesis is that differences in viral genes in influenza A are affecting the host immune responses that cause these differing severities. In our study we sought to create a time course mouse model in which we administered two different viruses: A/Puerto Rico/8/34- H1N1 (PR8) and A/swine/Texas/4199-2/98-H3N2 (TX98), along with a group A Streptococcus pyogenes isolate. Through morbidity and mortality analyses, viral lung titers, and bacterial lung and spleen titers we confirmed lethal (PR8) and non-lethal (TX98) phenotypes. The lung pathology results demonstrated that the super-infection progressed in a similar manner while the mortality, viral titers, and bacterial titers showed different disease burdens for the two viruses. This confirmed our hypothesis that there are viral genes controlling the host immune response that created the two phenotypes. Importantly, two phenotypes emerged from this work which led us to develop the hypothesis that one or more of the 8 individual influenza gene segments determine the severity of influenza:GAS super-infections. Future plans include utilizing reverse genetics to create gene segment reassortants of the lethal PR8 (H1N1) influenza virus and the nonlethal TX98 (H3N2) influenza virus.
Watson, Trevor, "A time course study of Influenza A and Streptococcus pyogenes secondary super- infections in a mouse model." (2013). Honors Thesis. 209.