Presentation Type
Poster
Faculty Mentorā€™s Full Name
Stephen Lodmell
Faculty Mentorā€™s Department
Department of Biological Sciences and Biochemistry
Abstract / Artist's Statement
The cellular innate immune response is the first line of defense against viral infection. A robust response is necessary to fight infection, but an overblown response can kill the cell and damage surrounding tissue. Understanding how the innate response is regulated can elucidate better means of preventing and ending viral infections. Rift Valley fever virus (RVFV), an RNA virus, is a pathogen of particular importance due to its deadly effects on domestic livestock and humans. Our lab investigates RVFV's effects on proteins involved in the cell's innate antiviral response. Although the precise roles of RIOK3 remain controversial, it has been determined to affect the type-1 interferon (IFN) response. Results from our lab showed that RIOK3 helps mount an IFN response in epithelial cells, but it was recently suggested by another group that RIOK3 plays a role in suppressing the interferon response in immune cells. In their model, RIOK3 acts as a guide for the protein TRIM40, an E3-ubiquitin ligase that targets other proteins for proteolytic degradation. In particular, the immune cell model suggested RIOK3 led TRIM40 to ubiquitinate MDA5 for destruction. Since MDA5 usually plays a role in mounting the IFN response, targeting MDA5 would blunt the response. Interestingly, TRIM40 is not typically expressed in epithelial cells but in immune cells. Therefore, we hypothesized that the expression of TRIM40 in our epithelial cells in culture would affect their IFN response. To test this hypothesis, immortalized human embryonic kidney cells (HEK-293) were transfected with vectors expressing the protein TRIM40. Cells were immune stimulated using poly(I:C), a potent IFN inducer that mimics viral RNA. We compared expression levels of MDA5 in the cells expressing TRIM40 to control cells by immunoblotting. Additionally, HEK-293s were transfected with TRIM40 and then infected with RVFV (MP12), and expression of IFN-š¯›½ was assayed by RT-qPCR. The results of my experiments showed no comparative decrease in cells' expression of MDA5 when TRIM40 was present and no difference in expression of IFN-š¯›½ during infection when TRIM40 was overexpressed. Collectively, these results suggest some mechanism other than TRIM40 expression alone is responsible for the other group's observed suppression of the IFN response by RIOK3 in immune cells.
Category
Life Sciences
Role of RIOK3 in Innate Immunity
UC South Ballroom
The cellular innate immune response is the first line of defense against viral infection. A robust response is necessary to fight infection, but an overblown response can kill the cell and damage surrounding tissue. Understanding how the innate response is regulated can elucidate better means of preventing and ending viral infections. Rift Valley fever virus (RVFV), an RNA virus, is a pathogen of particular importance due to its deadly effects on domestic livestock and humans. Our lab investigates RVFV's effects on proteins involved in the cell's innate antiviral response. Although the precise roles of RIOK3 remain controversial, it has been determined to affect the type-1 interferon (IFN) response. Results from our lab showed that RIOK3 helps mount an IFN response in epithelial cells, but it was recently suggested by another group that RIOK3 plays a role in suppressing the interferon response in immune cells. In their model, RIOK3 acts as a guide for the protein TRIM40, an E3-ubiquitin ligase that targets other proteins for proteolytic degradation. In particular, the immune cell model suggested RIOK3 led TRIM40 to ubiquitinate MDA5 for destruction. Since MDA5 usually plays a role in mounting the IFN response, targeting MDA5 would blunt the response. Interestingly, TRIM40 is not typically expressed in epithelial cells but in immune cells. Therefore, we hypothesized that the expression of TRIM40 in our epithelial cells in culture would affect their IFN response. To test this hypothesis, immortalized human embryonic kidney cells (HEK-293) were transfected with vectors expressing the protein TRIM40. Cells were immune stimulated using poly(I:C), a potent IFN inducer that mimics viral RNA. We compared expression levels of MDA5 in the cells expressing TRIM40 to control cells by immunoblotting. Additionally, HEK-293s were transfected with TRIM40 and then infected with RVFV (MP12), and expression of IFN-š¯›½ was assayed by RT-qPCR. The results of my experiments showed no comparative decrease in cells' expression of MDA5 when TRIM40 was present and no difference in expression of IFN-š¯›½ during infection when TRIM40 was overexpressed. Collectively, these results suggest some mechanism other than TRIM40 expression alone is responsible for the other group's observed suppression of the IFN response by RIOK3 in immune cells.