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Most infections are asymptomatic (90\u201395%), but symptoms can be as severe as hemorrhagic fever and encephalitis. One recently emerged flavivirus is Zika virus (ZIKV), which was originally isolated from rhesus monkeys in Uganda roughly 70 years ago but has recently spread east, reaching S. America in 2015\u20132016. This outbreak was associated with the development of Guillain\u2013Barr\u00e9 syndrome in adults and microcephaly in infants born to expectant mothers infected early in pregnancy. ZIKV must traverse the placenta to impact the development of the fetus, but the mechanisms responsible are unknown. While flaviviruses are known to disrupt splicing patterns in host cells, little is known about how flaviviruses such as ZIKV impact the alternative polyadenylation (APA) of host transcripts. This is important as APA is well-established as a mechanism in the regulation of mRNA metabolism and translation. Thus, we sought to characterize transcriptomic changes including APA in human placental (JEG3) cells in response to ZIKV infection using Poly(A)-ClickSeq (PAC-Seq). We used our differential Poly(A)-cluster (DPAC) analysis pipeline to characterize changes in differential gene expression, alternative poly-adenylation (APA) and the use of alternative terminal exons. We identified 98 upregulated genes and 28 downregulated genes. Pathway enrichment analysis indicated that many RNA processing and immune pathways were upregulated in ZIKV-infected JEG3 cells. We also updated DPAC to provide additional metrics of APA including the percentage-distal usage index (PDUI), which revealed that APA was extensive and the 3\u2032 UTRs of 229 genes were lengthened while 269 were shortened. We further found that there were 214 upregulated and 59 downregulated poly(A)-clusters (PACs). We extracted the nucleotide sequences surrounding these PACs and found that the canonical signals for poly-adenylation (binding site for poly-A binding protein (PABP) upstream and a GU-rich region down-stream of the PAC) were only enriched in the downregulated PACs. These results indicate that ZIKV infection makes JEG3 cells more permissive to non-canonical poly-adenylation signals.<\/jats:p>","DOI":"10.3390\/pathogens11080936","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T23:28:41Z","timestamp":1660865321000},"page":"936","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Zika Virus Infection Alters Gene Expression and Poly-Adenylation Patterns in Placental Cells"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3681-3639","authenticated-orcid":false,"given":"Stephanea L.","family":"Sotcheff","sequence":"first","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Yun-Chung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Elrod","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0211-9227","authenticated-orcid":false,"given":"Jun","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Beijing Key Laboratory of Environmental and Viral Oncology, Faculty of Environment and Life, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Jaworski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-5861","authenticated-orcid":false,"given":"Mug\u00e9 N.","family":"Kuyumcu-Martinez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Yong","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Sealy Institute for Drug Discovery, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2874-5990","authenticated-orcid":false,"given":"Andrew L.","family":"Routh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.antiviral.2008.05.004","article-title":"Closing the door on flaviviruses: Entry as a target for antiviral drug design","volume":"80","author":"Perera","year":"2008","journal-title":"Antiviral. 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