Zika and dengue viruses differentially modulate host mRNA processing factors defining its virulence

Changes in global climate have contributed to increased tick and mosquito (vector) populations and subsequent vector-borne flavivirus infections in humans. This increase poses a threat to the safety of human-derived biologics such as cell and gene therapy. We conducted time-course transcriptomic and protein analyses to uncover host molecular factors driving the virulence of Zika virus (ZIKV) and Dengue virus (DENV) in relation to host defense mechanisms, as these viruses have caused recent flavivirus outbreaks. Compared to DENV, ZIKV exhibited stronger virulence and cytopathic effects. RNA-seq analysis revealed differential expression of various cellular factors, including RNA processing factors. Protein analysis showed ZIKV, unlike DENV, degrades nonsense-mediated RNA decay (NMD) factors in host cells, resulting in accumulated host intronic transcripts. We found that active nuclear transport is required for ZIKV replication. From our findings, we hypothesize that ZIKV drives early host cell cytopathy through targeted protein degradation. Studies are underway to develop novel strategies to detect flaviviruses in biologics based on transcriptomics and proteomics.