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Examination of Factors Influencing Environmental Stability of the 2009 H1N1 Pandemic Influenza Virus and its Pathogenesis in the Ferret Model

French, Andrea Jane (2023) Examination of Factors Influencing Environmental Stability of the 2009 H1N1 Pandemic Influenza Virus and its Pathogenesis in the Ferret Model. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Influenza virus is an ongoing global disease burden. It circulates annually as a seasonal respiratory virus and has caused most major pandemics within the last century. Influenza infection is often complicated by secondary bacterial infection with Streptococcus pneumoniae, resulting in increased morbidity and mortality. This dissertation investigates factors influencing transmission and severe disease of the 2009 H1N1 pandemic influenza virus (H1N1pdm09) by assessing how co-infection with S. pneumoniae impacts H1N1pdm09 pathogenesis and environmental stability and by defining the role of droplet size on H1N1pdm09 environmental stability. First, research investigating co-infection’s impact on morbidity established tissue-specific trends towards increased bacterial burden in the upper respiratory tract of co-infected ferrets compared to mono-infection. The relationship between viral and bacterial burden varied by tissue and was associated with altered host responses. Exploration of host responses showed that they were critical components of increased morbidity during co-infection and the altered host responses varied by tissue. These data establish previously unknown aspects of pathogenesis and host immune response to influenza virus and S. pneumoniae co-infection in the ferret model. Additional work focusing on the environmental persistence and prevalence of H1N1pdm09 and S. pneumoniae in respiratory emissions revealed that both microbes were detected in aerosols from co-infected ferrets. In addition, S. pneumoniae in respiratory fluid droplets exhibited a trend towards increased persistence in the presence of H1N1pdm09. Co-infections with these microbes can therefore result in spread of both pathogens and may lead to increased bacterial stability outside the host. Finally, to evaluate virus persistence, I compared H1N1pdm09 decay in 50 µL, 5 µL, and 1 µL droplets at variable relative humidity to decay of bacteriophage Phi6. Results show virus within larger droplets is more sensitive to relative humidity-mediated decay than smaller droplets. Additionally, Phi6 decay differed from H1N1pdm09 at low relative humidity. These findings highlight the importance of using relevant droplet sizes and appropriate surrogates to evaluate half-lives for pathogens. Taken together, the results of this dissertation further the field of influenza virus transmission and pathogenesis and can ultimately inform future mitigation measures to reduce overall disease burden.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
French, Andrea Janeanf142@pitt.eduanf1420000-0002-1210-4857
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorLakdawala, Seemaseema.s.lakdawala@emory.edu0000-0002-7679-2150
Committee ChairFlynn, JoAnnejoanne@pitt.edu0000-0001-7874-8981
Committee MemberHiller, N. Luisalhiller@andrew.cmu.edu0000-0001-6572-1368
Committee MemberWilliams, Johnjvw@pitt.edu0000-0001-8377-5175
Committee MemberBomberger, JenniferJennifer.M.Bomberger@dartmouth.edu0000-0003-4767-6238
Committee MemberMyerburg, Mikemyerburgm@upmc.edu0000-0003-1417-2906
Date: 4 October 2023
Date Type: Publication
Defense Date: 14 April 2023
Approval Date: 4 October 2023
Submission Date: 18 May 2023
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 181
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Microbiology and Immunology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: influenza virus, Streptococcus pneumoniae, stability, persistence, aerosol, transmission, co-infection, pathogenesis
Date Deposited: 04 Oct 2023 18:29
Last Modified: 04 Oct 2023 18:29


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