The Chande Lab Reveals Key HIV Mechanism Linking Vpr to TGF-beta Signaling
The research group of Dr. Ajit Chande (Department of Biological Sciences) has identified a previously unrecognized mechanism by which HIV-1 Vpr activates the TGF-beta signaling pathway. In their study published in PLOS Pathogens, the authors demonstrate that the HIV-1 accessory protein Vpr induces TGF-beta production, which in turn drives the upregulation of the circular RNA ciTRAN, implicating a novel link between viral factors, host signaling, and circRNA regulation. Importantly, the pathogenic relevance of Vpr-induced TGF-beta signaling has now been independently reinforced by a recent study in Science Translational Medicine (Cai et al., 2026). This work shows that HIV-1 Vpr promotes the conversion of a subset of CD4+ T cells into CD8+ T cells through upregulation of TGF-beta1, with TGF-beta–dependent signaling being essential for CD8 lineage reprogramming. These induced CD8+ T cells exhibit a regulatory-like phenotype and retain the capacity to harbor latent HIV-1, identifying them as a previously unrecognized viral reservoir. Together, these findings position the Vpr–TGF-beta axis as a mediator of HIV-1 pathogenesis, linking viral manipulation of host signaling to both transcriptional regulation and immune cell reprogramming. This convergence highlights TGF-beta signaling as a compelling target for strategies aimed at limiting viral persistence and addressing the latent reservoir. For more details, kindly visit https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013332.
