TRIM28 co-localizes with CDK9. Image credit: Ma et al. (CC BY 4.0)
The human immunodeficiency virus-1, or HIV-1, infects certain human cells, including white blood cells. One reason the infection is incurable is because the virus can integrate its genetic information into its host, and essentially ‘sleep’ within the host cell, a process called latency. This helps to hide HIV-1 from the immune system and stops it getting destroyed.
Latency represents a critical challenge in treating and curing HIV-1. One proposed cure for HIV-1 involves ‘shocking’ the viruses out of latency so that they can be eliminated. Applying this so-called shock and kill approach means scientists need to understand more about how latency is maintained. Previous evidence shows that latency requires proteins known as histone deacetylases and histone methyltransferases. Certain gene-silencing proteins called transcription suppressors are also involved.
Ma et al. have now examined latent HIV-1 in several kinds of human cells grown in the laboratory. The cells were modified to make certain proteins at much lower levels than normal. The experiments showed that the loss of a protein called TRIM28 ‘wakes up’ latent HIV-1. TRIM28 attaches chemical marks called SUMOylations to gene regulators in the cell. These SUMOylations restrict the activity of HIV-1’s genes, which is important to maintain latency. Specifically, TRIM28 adds SUMOylations to a protein named CDK9 at three key positions.
Reducing the levels of TRIM28 made it easier to shock many HIV-1 in infected cells out of latency. With further investigation, targeting TRIM28 may one day be used to treat HIV-1 infection through a shock and kill method.
