HSV-1 stimulation-related protein HSRG1 inhibits viral gene transcriptional elongation by interacting with Cyclin T2
Open accessAbstract
The protein encoded by HSRG1 (HSV-1 stimulation-related gene 1) is a virally induced protein expressed in HSV-1-infected cells. We have already reported that HSRG1 is capable of interacting with transcriptional regulator proteins. To further analyze the effects of HSRG1 on the regulation of viral gene transcription, we expressed the HSRG1 protein in transfected cells and found that it postpones the proliferation of HSV-1. CAT (chloramphenicol acetyltransferase) assays also revealed that HSRG1 reduces transcription from HSV-1 promoters. Yeast two-hybrid and immunoprecipitation assays indicated that HSRG1 interacts with Cyclin T2, the regulatory subunit of P-TEFb, which is required for transcription elongation by RNA Pol II (RNAP II), and that amino acid residues 1-420 in Cyclin T2 are important for binding with HSRG1. Fluorescence assays suggested that the cellular localizations of those two proteins are influenced by their interaction. Further analyses with CAT assays revealed that HSRG1 inhibits the transcriptional activation by Cyclin T2 of viral promoters. Our results suggested that the inhibitory effects of HSRG1 on viral replication and proliferation are probably induced by its binding to Cyclin T2. Therefore, it is likely that HSRG1 inhibits viral gene transcriptional elongation by interacting with Cyclin T2.
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CCNT2 has been shown to be used by herpes simplex virus 1 (HSV-1) when it transcribes its genome.
“CCNT2 has also been shown to be used by herpes simplex virus 1 (HSV-1) when it transcribes its genome [46].”
From Multi-trait association studies discover pleiotropic loci between Alzheimer’s disease and cardiometabolic traits (2021) · cites this paper as [46]
Section 2.5 reports that Cyclin T2 increased transcriptional activity from HSV-1 promoters in transfected reporter assays, supporting a role in viral gene transcription. The paper infers a role during infection but does not directly show HSV-1 using Cyclin T2 to transcribe its genome. (LLM, conf=0.83)
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Cites
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Program, T. V. M. V., Bone, W. P., Siewert, K. M., Jha, A., Klarin, D., Damrauer, S. M., Chang, K.-M., Tsao, P. S., Assimes, T. L., Ritchie, M. D., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00773-z · Cited by 41 · see citing works
- Authors
- Wu, W., Yu, X., Li, W., Guo, L., Liu, L., Wang, L., & Li, Q.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Corresponding author
- Li, QiHan
- Venue
- Science China Life Sciences
- Published
- 2011-04
- Volume
- 54
- Issue
- 4
- Pages
- 359-365
- ISSN
- 1674-7305 (ISSN-L)
- 1869-1889
- OpenAlex
- W1980978677
- Cited by
- 5
- References
- 1
- Citations by year
- 2021: 2 · 2013: 2 · 2012: 1
- FWCI
- 0.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Science China Life Sciences (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30670094)
- Ministry of Education of the People's Republic of China
- Topics
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- herpes simplex virus type 1, P-TEFb, transcription elongation, viral transcription, RNA polymerase II, protein-protein interaction, viral replication inhibition, herpesvirus
- MeSH terms
- Animals, Chlorocebus aethiops, Cricetulus, Genes, Viral, Cricetinae, Humans, Promoter Regions, Genetic, Proteins, Transcription, Genetic, Vero Cells, Virus Replication, Gene Expression Regulation, Viral, CHO Cells, Herpesvirus 1, Human, Two-Hybrid System Techniques, Intracellular Signaling Peptides and Proteins, Cyclin T
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