PMID- 36069548 OWN - NLM STAT- MEDLINE DCOM- 20220930 LR - 20221024 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 96 IP - 18 DP - 2022 Sep 28 TI - A Novel, Fully Spliced, Accessory Gene in Equine Lentivirus with Distinct Rev-Responsive Element. PG - e0098622 LID - 10.1128/jvi.00986-22 [doi] LID - e00986-22 AB - All lentiviruses encode the accessory protein Rev, whose main biological function is to mediate the nuclear export of unspliced and incompletely spliced viral transcripts by binding to a viral cis-acting element (termed the Rev-responsive element, RRE) within the env-encoding region. Equine infectious anemia virus (EIAV) is a member of the lentivirus genus in the Retroviridae family and is considered an important model for the study of lentivirus pathogenesis. Here, we identified a novel transcript from the EIAV genome that encoded a viral protein, named Mat, with an unknown function. The transcript mat was fully spliced and comprised parts of the coding regions of MA and TM. Interestingly, the expression of Mat depended on Rev and the chromosome region maintenance 1 (CRM1) pathway. Rev could specifically bind to Mat mRNA to promote its nuclear export. We further identified that the first exon of Mat mRNA, which was located within the Gag-encoding region, acted as an unreported RRE. Altogether, we identified a novel fully spliced transcript mat with an unusual RRE, which interacted with Rev for nuclear export through the CRM1 pathway. These findings updated the EIAV genome structure, highlighted the diversification of posttranscriptional regulation patterns in EIAV, and may help to expand the understanding of gene transcription and expression of lentivirus. IMPORTANCE In lentiviruses, the nuclear export of viral transcripts is an important step in controlling viral gene expression. Generally, the unspliced and incompletely spliced transcripts are exported via the CRM1-dependent export pathway in a process mediated by the viral Rev protein by binding to the Rev-responsive element (RRE) located within the Env-coding region. However, the completely spliced transcripts are exported via an endogenous cellular pathway, which was Rev independent. Here, we identified a novel fully spliced transcript from EIAV and demonstrated that it encoded a viral protein, termed Mat. Interestingly, we determined that the expression of Mat depended on Rev and identified that the first exon of Mat mRNA could specifically bind to Rev and be exported to the cytoplasm, which suggested that the first exon of Mat mRNA was a second RRE of EIAV. These findings provided important insights into the Rev-dependent nuclear export of completely spliced transcripts in lentiviruses. FAU - Zhang, Xiangmin AU - Zhang X AD - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China. FAU - Li, Jiwei AU - Li J AD - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China. FAU - Zhang, Mengmeng AU - Zhang M AD - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China. FAU - Bai, Bowen AU - Bai B AD - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China. FAU - Ma, Weiwei AU - Ma W AD - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China. FAU - Lin, Yuezhi AU - Lin Y AD - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China. FAU - Guo, Xing AU - Guo X AD - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China. FAU - Wang, Xue-Feng AU - Wang XF AUID- ORCID: 0000-0002-5564-2487 AD - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China. FAU - Wang, Xiaojun AU - Wang X AUID- ORCID: 0000-0003-4521-4099 AD - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220907 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Gene Products, rev) RN - 0 (RNA, Messenger) RN - 0 (RNA, Viral) SB - IM MH - Animals MH - *Gene Products, rev/genetics MH - Horses MH - *Infectious Anemia Virus, Equine/metabolism MH - *Lentiviruses, Equine MH - RNA Splicing MH - RNA, Messenger/genetics MH - RNA, Viral/genetics PMC - PMC9517694 OTO - NOTNLM OT - EIAV OT - HIV-1 OT - Mat OT - RRE OT - Rev OT - lentiviruses OT - transcript OT - transcriptional regulation COIS- The authors declare no conflict of interest. EDAT- 2022/09/08 06:00 MHDA- 2022/10/01 06:00 PMCR- 2022/09/07 CRDT- 2022/09/07 09:03 PHST- 2022/09/08 06:00 [pubmed] PHST- 2022/10/01 06:00 [medline] PHST- 2022/09/07 09:03 [entrez] PHST- 2022/09/07 00:00 [pmc-release] AID - 00986-22 [pii] AID - jvi.00986-22 [pii] AID - 10.1128/jvi.00986-22 [doi] PST - ppublish SO - J Virol. 2022 Sep 28;96(18):e0098622. doi: 10.1128/jvi.00986-22. Epub 2022 Sep 7.