Commun Biol. 2024 Nov 16;7(1):1521. doi: 10.1038/s42003-024-07139-9.
ABSTRACT
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.
PMID:39550519 | DOI:10.1038/s42003-024-07139-9
