News from DCEXS-UPF
Human Immunodeficiency Virus (HIV) latency, its ability to remain dormant within infected cells and thus invisible to antiviral drugs and the immune system, is a major hurdle to curing HIV infection. Now, researchers from the Infection Biology Laboratory at UPF, the IrsiCaixa AIDS Research Institute and the National Institute of Infectious Diseases (NIID) in Japan, have discovered a mechanism by which HIV may escape from latency reversal and thus remain in a dormant state.
In their study now published in Frontiers in Microbiology, the researchers, led by Yasuko Tsunetsugu-Yokota, explored the relationship between sense and antisense transcription in HIV. They observed that some of the latently-infected cells expressed antisense transcripts which exhibited suppressor activity and locked the integrated provirus in a non-reactivable state. Andreas Meyerhans, ICREA research professor at UPF, explains “This study not only defines a new type of latent HIV-infected cells but also hints at novel therapy options”, something he and his fellow ICREA research professor Christian Brander at Irsicaixa have been exploring for a while now.
By enhancing antisense transcription and vaccinating infected individuals with antisense-encoded proteins, infected cells may be eliminated before they ever become virus producers. This is a strategy that is under evaluation for the other human retrovirus, HTLV. “A clinically feasible way to continue investingating along these lines, however, has yet to be defined”, concludes Mie Kobayashi-Ishihara, first author of the study.
Kobayashi-Ishihara M, Terahara K, Martinez JP, Yamagishi M, Iwabuchi R, Brander C, Ato M, Watanabe T, Meyerhans A and Tsunetsugu-Yokota Y. HIV LTR-driven antisense RNA by itself has regulatory function and may curtail virus reactivation from latency. Frontiers in Microbiology. May, 2018. doi: 10.3389/fmicb.2018.01066