Zika (ZIKV) viral infection continues to be a growing concern for inhabitants of the southern United States, Puerto Rico, and the Carribean. Infection in pregnant women can often lead to microcephaly in the resulting children. According to the CDC, 2,364 pregnant women in the United States had lab evidence of ZIKV infection in 2017. The possibility of ZIKV being spread to the rest of the southern United States is a threat to many pregnant individuals and a concern for those looking to conceive; making the need to understand how ZIKV causes microcephaly critically important. The ZIKV congenital microcephaly mimics a rare genetic disorder, Progressive Cerebello-Cerebral Atrophy (PCCA). This disorder is characterized by a knockdown of the expression of selenoproteins, resulting in a lack of micronutrient selenium to the brain; which is essential for neuronal development. Our preliminary data has already identified a segment of ZIKV RNA which has the potential for antisense interaction with host cellular mRNAs of selenoproteins Thirodoxin Reductase (TR1) and Selenoprotein P (SePP1). Our results suggest that this interaction is possible through computer modeling and gel shift assays. Our group hypothesizes that ZIKV RNA has an affinity for host cellular mRNAs coding for the expression of selenoproteins, and that an antisense-mediated interaction between these two species is occurring. This resulting interference with selenium-host biochemistry may mimic the loss of selenoproteins due to the genetic defect of PCCA, giving insight into why ZIKV infection in pregnant women can cause microcephaly in the resulting children. The goal of this study is to address the gap in knowledge surrounding how ZIKV causes microcephaly. With information gathered from this study, possible avenues to circumvent the mechanism and prevent the onset of microcephaly could be opened up to further study.

Antisense-mediated knockdown of host selenoprotein expression in ZIKV infected cells via targeting of cellular mRNA by viral RNA

256th National Meeting (2018)

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