Verifying Models and Identifying New Targets for Attacking HIV Latency
By Jeffrey Laurence, M.D.
Study co-author Dr. Steve YuklIn order to identify potential new ways to overcome HIV latency—the main obstacle to an HIV cure—researchers would ideally study latently infected cells from people living with HIV. Yet the use of latently infected cells taken directly from an infected person has limitations of scale, and cells from tissues other than blood are not easily accessible. The degree to which various test-tube systems for HIV latency accurately reflect what’s happening in an infected person’s cells is unclear, hampering the search for relevant treatments. Therefore, researchers must develop model test-tube systems that recapitulate persistent HIV in people.
Three test-tube cell models were compared to blood cells obtained from HIV-positive individuals on antiretroviral treatment with undetectable viral loads. All models were able to recapitulate the molecular patterns by which HIV appears to maintain a dormant state. In addition, a common set of some 200 host genes distinguished latently infected cells from cells activated to produce infectious virus in all these cell systems. There was a particular focus on the conversion of HIV DNA into messenger RNA, an early step in the process of making HIV proteins.
The authors concluded that the genes they identified may represent new targets for treatments designed to silence or activate HIV reservoir cells.
amfAR was a funder of this research.
Dr. Laurence is amfAR’s senior scientific consultant.