News & Events

When

Date - March 17, 2021
1:00 pm - 2:00 pm

What

Dissertation Title: Zika mediated knockdown of host selenoprotein expression via antisense interactions between Zika RNA and host cell mRNAs as a compounding factor in the onset of Zika related congenital microcephaly

Advisor: Dr. Will Taylor

Abstract:

Selenium status plays a major role in health impacts of various RNA viruses. We recently reported potential antisense interactions between viral mRNAs and host mRNAs of the antioxidant selenoprotein thioredoxin reductase (TR). Here, we examine possible targeting of selenoprotein mRNAs by Zika virus (ZIKV) as a pathogenic mechanism, because microcephaly is a key manifestation of Progressive Cerebello-Cerebral Atrophy (PCCA), a genetic disease of impaired selenoprotein synthesis. Potential antisense matches between ZIKV and human selenoprotein mRNAs were initially identified via nucleotide BLAST searches, using ZIKV genomic RNA as a probe. The strongest antisense matches of ZIKV regions, against human TR1 and selenoprotein P (SePP1), were validated by algorithms for prediction of RNA hybridization and microRNA/target duplexes. Computationally, ZIKV has regions of extensive (~30bp) and stable (ΔE < −50kcal/mol) antisense interactions with mRNAs of both TR1 and SePP1, a selenium carrier protein essential for delivery of selenium to the brain. Western blot probe for SePP1 and TR1 expression as well as RT-qPCR analysis was conducted on non-ZIKV infected and ZIKV infected cells and effects of selenium supplementation on any protein or mRNA change in SePP1 and TR1 expression upon ZIKV infection was observed. ZIKV infection was shown to knock down SePP1 expression by 99.1% and TR1 expression by 90.4% in ZIKV infected cells. TR1 expression is improved upon selenium supplementation by 3.6% in a significant fashion but SePP1 expression is largely unaffected. SePP1 mRNA increases by 6 folds upon infection of ZIKV, and TR1 mRNA increases nearly 8 fold with ZIKV infection and selenium supplementation. These findings provide more insight into how ZIKV infection can lead to microcephaly onset and how viral RNA and host cell RNA interactions serve as a key strategy for viral inhibition of host cell viral immune responses.