Transactivation of the novel 5’ cis-acting element of mouse mammary tumor virus (MMTV) by human retroviral transactivators Tat and Tax

• Published in: Communications biology Vol. 7; no. 1; pp. 1521 - 14
• Main Authors: Khader, Thanumol Abdul, Ahmad, Waqar, Akhlaq, Shaima, Panicker, Neena Gopinathan, Gull, Bushra, Baby, Jasmin, Rizvi, Tahir A., Mustafa, Farah
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-11-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/106; 13/109; 38; 38/22; 38/35; 38/70; 38/77; 38/90; 45; 45/44; 631/1647/2017/1958; 631/326/596/1787; 631/45/500; 631/61/2300/1514; 631/67/1858; 82; 82/29; 96/10; Biomedical and Life Sciences; Expression vectors; Gene therapy; HIV; Human immunodeficiency virus; Life Sciences; Nuclear transport; Regulatory sequences; RNA transport; Tat protein; Tumor viruses; Tumors
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-07139-9

The mouse mammary tumor virus (MMTV) encodes a 5’ element crucial for transcription of its genome along with the Rem/Rem-responsive element (RmRE) responsible for nuclear export of this unspliced RNA. Whether the 5’ element is Rem-responsive or has any functional interaction with host/viral factors to facilitate MMTV gene expression was tested in this study. Our results reveal that the 5’ element is non-responsive to Rem, but can be transactivated by both HIV Tat and HTLV-1 Tax activators. Reciprocally, MMTV could transactivate not only HIV TAR (similar to HTLV Tax), but also its 5’ element. Furthermore, we reveal involvement of pTEFb, a general elongation factor associated with transactivation by Tat/Tax. This makes MMTV the first
betaretrovirus
to encode both Rem/RRE and Tat/TAR-Tax/TRE-like transcription regulatory systems. This study should enhance not only our understanding of retrovirus replication and virally-induced cancers/immunodeficiency syndromes, but also development of improved retroviral vectors for human gene therapy.
The mouse mammary tumor virus (MMTV) encodes a gene transactivation system similar to HIV Tat/TAR-HTLV Tax/TRE that requires a yet-to-be identified virally-encoded factor and the cellular factor pTEF-b for function.