Defining role of different virus sensing pathways in modulating ZIKV replication in human Sertoli cells

Simple item page
dc.contributor.advisor Verma, Saguna
dc.contributor.author Jiyarom, Boonyanudh
dc.contributor.department Biomedical Sciences
dc.date.accessioned 2021-02-08T21:14:52Z
dc.date.issued 2020
dc.description.degree M.S.
dc.embargo.liftdate 2022-02-08
dc.identifier.uri http://hdl.handle.net/10125/73304
dc.subject Virology
dc.subject Immunology
dc.subject Cellular biology
dc.title Defining role of different virus sensing pathways in modulating ZIKV replication in human Sertoli cells
dc.type Thesis
dcterms.abstract ZIKV is shown to establish persistence in the testes; however, the mechanisms remain undefined. We recently demonstrated that ZIKV was able to replicate and persist in human Sertoli cells (SC), an important cell type of seminiferous tubules. In addition, our host transcriptomic data predicted RIG-I and TLR3 as the top virus sensing pathways modulated in SC, however the specific role and efficiency of these pathways in controlling ZIKV is not yet determined. Here, we elucidate the impact of blocking these critical antiviral pathways on ZIKV replication. TLRs and RLRs were inhibited using siRNA or small molecule inhibitors in SC and infected with ZIKV PRVABC59. A549 cells were used as controls in some experiments. Data demonstrated that the independent inhibition of both RIG-I and MDA5, but not TLR3 nor TLR7 signaling increased ZIKV replication. Gene expression of IFNβ showed no change in both siMDA5 and siRIG-I SC, however, there was a reduction in the activation of IRF3 and MXA expression in these PRR deficient SC. Further, we observed that exogenous IFNβ treatment significantly reduced ZIKV titers in SC that was comparable to A549, thus indicating that IFN signaling is active in SC. To delineate the crosstalk of PRRs with other immunosuppressive pathways in the testes, SC were pretreated with TGFβ superfamily members molecules (TGFβ, Activin A, and BMP6) and virus titers measured. We first showed that ZIKV does not induce changes in TGFβ and Activin A mRNA expression. Additionally, there was no change in ZIKV titers in TGFβ and Activin A treated SC. However, ZIKV downregulated BMP6 at later time points of infection and the exogenous BMP6 treatment decreased ZIKV in these cells SC. Interestingly, treatment of BMP6 resulted in an increased in both RIG-I and MDA5 in ZIKV infected SC at 120hpi. Our data suggest that downregulation of BMP6 and downstream signaling by ZIKV at later stages of infection may modulate functioning of antiviral response and facilitate virus persistence. Collectively, these results fill in gaps in our understanding of the antiviral signaling mechanisms underlying ZIKV infection and persistence in human testes.
dcterms.extent 111 pages
dcterms.language en
dcterms.publisher University of Hawai'i at Manoa
dcterms.rights All UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.
dcterms.type Text
local.identifier.alturi http://dissertations.umi.com/hawii:10892
Files
Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Jiyarom_hawii_0085O_10892.pdf
Size:
7.61 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
M.S. - Biomedical Sciences