HIV latency

Enhanced transmission electron micrograph (TEM) of the virus (HIV) responsible for AIDS. Credit: James Cavallini

Summary of the article A CRISPR Screen of HIV Dependency Factors Reveals That CCNT1 Is Non-Essential in T Cells but Required for HIV-1 Reactivation from Latency. Hafer TL, Felton A, Delgado Y, Srinivasan H, Emerman M. Viruses. 2023 Aug 31;15(9):1863. doi: 10.3390/v15091863. PMID: 37766271

HIV is the virus responsible for the AIDS disease. Its genetic material is integrated into the DNA of the host cell (human immune cells) where it gets replicated along with the DNA of the host.  In rare cases, it also becomes integrated without actively producing new viruses in what is known as the latency/resting state (latent HIV infection), which may become active at some later time.  Even though active virus replication can be effectively suppressed with potent antiviral therapy, the ability to remain latent is what prevents HIV from being completely cured from the body.

A group of proteins from the host cell are essential for the replication of the virus; they are called Dependency Factors. This study focused on these Dependency Factors and their role in the latency state. It was found that some of these factors, especially one named CCNT1, play an essential role in reactivating the virus from its latency stage. In other words, these factors can reverse the latency state to an active state. Reversing the latency state (also known as reactivation from latency or latency reversal) would mean the virus starts actively replicating, allowing the immune system to recognize and eliminate the infected cell.

The study found that the genes responsible for these Dependency Factors can be silenced (in what is known as gene knockout), thereby preventing the activation of the virus from the latent state.

These results suggest that, by silencing these Dependency Factors, one can effectively inhibit the reactivation of the virus, thereby preserving the latent stage and potentially inactivating the virus from emerging from latency and resuming active replication.

Thus, the Dependency Factor CCNT1 is a promising therapeutic target for locking HIV into a more permanent latency and ultimately achieving HIV cure.