The host antiviral ribonuclease L protein supports Zika virus replication factory formation to enhance infectious virus production

Jillian N Whelan; Joshua Hatterschide; David M. Renner; Beihua Dong; Robert H Silverman; Susan R Weiss

RNase L-mediated rRNA degradation, which was only detectable in ZIKV infected +RL 312 WT cells and not VC or +RL R667A cells, despite OAS3 protein expression in all three 313 cell lines (Figure 6A&B) . We evaluated effects of RNase L WT or R667A expression on 314 ZIKV dsRNA expression and localization compared to that of VC cells at 20hpi, using PDI 315 ER staining to denote RF sites. We found that expression of either RL WT or RL R667A 316 increased ZIKV dsRNA intensity at the ER over that in VC cells, however only RL R667A 317 increased circularity of ZIKV RFs in comparison to those of VC cells (Figure 6C&D) . To 318 determine if RNase L effects on ZIKV dsRNA intensity or circularity correlated with 319 elevated infectious ZIKV titers, we measured virus from infected HeLa M cells at 48hpi 320 and detected a significant increase in ZIKV production in RL R667A-expressing cells 321 compared to VC or RL WT-expressing cells (Figure 6E ). In addition, we found that neither 322 All rights reserved. No reuse allowed without permission.