Regulation of Rev expression by the equine infectious anaemia virus tat-rev mRNA Kozak sequence and its potential influence on viral replication.
Abstract: Rev, an important accessory protein of equine infectious anaemia virus (EIAV), induces the nuclear export of incompletely spliced viral mRNAs. Rev is translated from the tat-rev mRNA through leaky scanning of the tat CUG. In this study, the function of the Kozak sequence at the beginning of the rev ORF was investigated. Deletion or attenuation of the Kozak sequence resulted in expression of an N-terminal 11 aa-truncated Rev in addition to WT Rev. Truncated Rev displayed weaker promotion of Gag expression and processing than WT Rev. Furthermore, EIAV rescued from an infectious molecular clone (pEIAVUK3) with Kozak attenuation exhibited decreased viral replication in host cells in vitro. These results provide a new understanding of the relationship between EIAV Rev expression and viral replication.
Publication Date: 2016-07-13 PubMed ID: 27411804DOI: 10.1099/jgv.0.000548Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article discusses how the control of Rev protein expression in the Equine Infectious Anemia Virus (EIAV) through the Kozak sequence in the virus’s mRNA could potentially influence the virus’s ability to replicate.
Study Overview
- The scientists conducted research on the EIAV – a virus that infects horses, similar to how HIV infects humans. Just like HIV, EIAV is a lentivirus and has a similar replication cycle.
- The study focuses on one of the proteins encoded by the EIAV called Rev.
Role of Rev and Kozak sequence
- The Rev protein plays an essential role in the virus’s replication cycle. It promotes the transportation of the virus’s mRNA (genetic material) from the cell’s nucleus to the cytoplasm. This step is vital for the virus to successfully create more viral proteins and ultimately more virus particles.
- Rev is produced from the tat-rev mRNA through a process called leaky scanning. This mechanism is involved in controlling the production (translation) of proteins from mRNA.
- The Kozak sequence is a region of mRNA, located near the start of the part that codes for a protein. It plays a critical role in initiating the translation process.
Findings in the study
- The researchers manipulated the Kozak sequence at the beginning of the rev coding sequence and observed its effects on the production of the Rev protein and the virus’s ability to replicate.
- When the Kozak sequence was deleted or weakened, the virus still produced the Rev protein, but it had a truncation (missing piece) at the beginning. This truncated form of Rev was less effective in promoting the expression and processing of another viral protein, Gag.
- Moreover, the researchers restored viral replication in an infectious molecular clone with a weakened Kozak sequence. The resultant EIAV showed decreased viral replication in host cells in vitro (in a controlled laboratory environment).
Significance of the Study
- The results suggest that the Kozak sequence in the EIAV’s tat-rev mRNA plays a significant role in regulating the production of the Rev protein and, consequently, the virus’s replication.
- This novel finding extends our understanding of how viruses control their protein production, a crucial aspect of their lifecycle. This knowledge could potentially be harnessed for developing antiviral strategies.
Cite This Article
APA
Ma J, Zhang Z, Yao Q, Su C, Yin X, Wang X.
(2016).
Regulation of Rev expression by the equine infectious anaemia virus tat-rev mRNA Kozak sequence and its potential influence on viral replication.
J Gen Virol, 97(9), 2421-2426.
https://doi.org/10.1099/jgv.0.000548 Publication
Researcher Affiliations
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, PR China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, PR China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, PR China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, PR China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, PR China.
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, PR China.
MeSH Terms
- Cell Line
- Gene Expression Regulation, Viral
- Gene Products, rev / biosynthesis
- Gene Products, rev / genetics
- Gene Products, tat / biosynthesis
- Humans
- Infectious Anemia Virus, Equine / genetics
- Protein Biosynthesis
- RNA, Messenger / metabolism
- Virus Replication
Citations
This article has been cited 1 times.- Ren H, Yin X, Su C, Guo M, Wang XF, Na L, Lin Y, Wang X. Equine lentivirus counteracts SAMHD1 restriction by Rev-mediated degradation of SAMHD1 via the BECN1-dependent lysosomal pathway.. Autophagy 2021 Oct;17(10):2800-2817.
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