Graduation Year
2017
Document Type
Dissertation
Degree
Ph.D.
Degree Name
Doctor of Philosophy (Ph.D.)
Degree Granting Department
Medical Sciences
Major Professor
Shyam S. Mpohapatra, Ph.D.
Committee Member
Nanjundan Meera, Ph.D.
Committee Member
Srinivas Baradwaj, Ph.D.
Committee Member
Kennet Ugen, Ph.D.
Committee Member
Andreas Seyfang, Ph.D.
Keywords
Respiratory Syncytial Virus (RSV), Interleukin 1 beta (IL-1β), osteopontin (OPN), CD44, Antiviral response, innate immunity
Abstract
The molecular mechanisms underlying susceptibility to severe respiratory syncytial virus (RSV) infection remain poorly understood. Herein, we report on the role of osteopontin (OPN) in regulation of RSV infection in human epithelial cells and how interleukin-1 beta (IL-1β), a cytokine secreted soon after RSV infection, when persistently expressed can induce OPN expression leading to increased viral infection. We first compared OPN expression in two human epithelial cell lines: HEK-293 and HEp-2. In contrast to HEp-2, HEK-293 expresses low levels of pro-caspase-1 resulting in decreased IL-1β expression in response to RSV infection. We found a correlation between low IL-1β levels and a delay in induction of OPN expression in RSV-infected HEK-293 cells compared to HEp-2. This phenomenon could partially explain the high susceptibility of HEp-2 cells to RSV infection versus the moderate susceptibility of HEK-293 cells. Also, HEK-293 cells expressing low levels of pro-caspase-1 exhibit decreased IL-1β expression and delayed OPN expression in response to RSV infection. HEK-293 cells incubated with human rIL-1β showed a dose-dependent increase in OPN expression upon RSV infection. Also, incubation with rOPN increased RSV viral load. Moreover, HEp-2 cells or mice infected with a mucogenic RSV strain RSV-L19F showed elevated levels of OPN in contrast to mice infected with the laboratory RSV strain rA2. This correlated with elevated levels of OPN following infection with RSV-L19F compared to rA2. Together, these results demonstrate that increased OPN expression is regulated in part by IL-1β, and the interplay between IL-1β and OPN signaling has a pivotal role in the spread of RSV infection.
Scholar Commons Citation
Sampayo-Escobar, Viviana, "osteopontin plays a pivotal role in in increasing severity of respiratory syncytial virus infection" (2017). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/6947
