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Journal of virology2022; 96(24); e0121022; doi: 10.1128/jvi.01210-22

Identification of a Novel Post-transcriptional Transactivator from the Equine Infectious Anemia Virus.

Abstract: All lentiviruses encode a post-transcriptional transactivator, Rev, which mediates the export of viral mRNA from the nucleus to the cytoplasm and which is required for viral gene expression and viral replication. In the current study, we demonstrate that equine infectious anemia virus (EIAV), an equine lentivirus, encodes a second post-transcriptional transactivator that we designate Grev. Grev is encoded by a novel transcript with a single splicing event that was identified using reverse transcription-PCR (RT-PCR) and RNA-seq in EIAV-infected horse tissues and cells. Grev is about 18 kDa in size, comprises the first 18 amino acids (aa) of Gag protein together with the last 82 aa of Rev, and was detected in EIAV-infected cells. Similar to Rev, Grev is localized to the nucleus, and both are able to mediate the expression of Mat (a recently identified viral protein of unknown function from EIAV), but Rev can mediate the expression of EIAV Gag/Pol, while Grev cannot. We also demonstrate that Grev, similar to Rev, specifically binds to rev-responsive element 2 (RRE-2, located in the first exon of mat mRNAs) to promote nuclear export of mat mRNA via the chromosome region maintenance 1 (CRM1) pathway. However, unlike Rev, whose function depends on its multimerization, we could not detect multimerization of Grev using coimmunoprecipitation (co-IP) or bimolecular fluorescence complementation (BiFC) assays. Together, these data suggest that EIAV encodes two post-transcriptional transactivators, Rev and Grev, with similar, but not identical, functions. Nuclear export of viral transcripts is a crucial step for viral gene expression and viral replication in lentiviruses, and this export is regulated by a post-transcriptional transactivator, Rev, that is shared by all lentiviruses. Here, we report that the equine infectious anemia virus (EIAV) encodes a novel viral protein, Grev, and demonstrated that Grev, like Rev, mediates the expression of the viral protein Mat by binding to the first exon of mat mRNAs via the chromosome region maintenance 1 (CRM1) pathway. Grev is encoded by a single-spliced transcript containing two exons, whereas Rev is encoded by a multiple-spliced transcript containing four exons. Moreover, Rev is able to mediate EIAV Gag/Pol expression by binding to rev-responsive element (RRE) located within the Env-coding region, while Grev cannot. Therefore, the present study demonstrates that EIAV encodes two post-transcriptional regulators, Grev and Rev, suggesting that post-transcriptional regulation patterns in lentivirus are diverse and complex.
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Publication Date: 2022-11-30 PubMed ID: 36448796PubMed Central: PMC9769392DOI: 10.1128/jvi.01210-22Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research focuses on the discovery of a new post-transcriptional transactivator, Grev, in the equine infectious anemia virus (EIAV), an equine lentivirus. This protein, similar to the well-known transactivator Rev, is fundamental in the process of transferring viral mRNA from the nucleus to the cytoplasm, a crucial part of viral gene expression and replication.

Understanding Post-transcriptional Transactivators

  • Post-transcriptional transactivators are crucial elements found in lentiviruses that function to transport viral mRNA from within the nucleus to the cytoplasm.
  • For viral gene expression and replication to take place, this transport process is vital.
  • All known lentiviruses encode for a transactivator known as Rev that executes this role.

The Discovery of Grev

  • The study shows that the equine infectious anemia virus (EIAV) encodes a second post-transcriptional transactivator, Grev.
  • Grev is now understood thanks to detailed analysis using reverse transcription-PCR and RNA-seq in EIAV-infected horse tissues and cells.
  • When compared to Rev, Grev has been recorded in the nucleus and can mediate the expression of Mat, a recently identified viral protein from EIAV. However, Grev is unable to mediate the expression of EIAV Gag/Pol, like Rev does.

Grev’s Function and Comparison with Rev

  • Grev similarly binds to the rev-responsive element 2 (RRE-2), promoting nuclear export of Mat mRNA via the chromosome region maintenance 1 (CRM1) pathway, much like Rev.
  • However, the functions of Rev require its capability to form multiples of itself (multimerization), a trait which has yet to be observed in Grev.

Grev and the Complexity of Lentiviral Post-transcriptional Regulation

  • The discovery and understanding of Grev highlight the complexity and diversity of the post-transcriptional regulation process in a lentivirus.
  • The fact that EIAV has two post-transcriptional regulators, Grev and Rev, shows that the process of viral gene expression and replication is multi-layered and involves more players than previously understood.

Cite This Article

APA
Li J, Zhang X, Bai B, Zhang M, Ma W, Lin Y, Wang X, Wang XF. (2022). Identification of a Novel Post-transcriptional Transactivator from the Equine Infectious Anemia Virus. J Virol, 96(24), e0121022. https://doi.org/10.1128/jvi.01210-22

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 96
Issue: 24
Pages: e0121022
PII: e01210-22

Researcher Affiliations

Li, Jiwei
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.
Zhang, Xiangmin
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.
Bai, Bowen
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.
Zhang, Mengmeng
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.
Ma, Weiwei
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.
Lin, Yuezhi
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.
Wang, Xiaojun
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.
Wang, Xue-Feng
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, China.

MeSH Terms

  • Animals
  • Equine Infectious Anemia / virology
  • Exons
  • Gene Products, rev / genetics
  • Horses / genetics
  • Infectious Anemia Virus, Equine / genetics
  • Infectious Anemia Virus, Equine / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Gene Expression Regulation, Viral / genetics

Conflict of Interest Statement

The authors declare no conflict of interest.

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Citations

This article has been cited 3 times.
  1. Wang XF, Zhang X, Ma W, Li J, Wang X. Host cell restriction factors of equine infectious anemia virus. Virol Sin 2023 Aug;38(4):485-496.
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