Exploring New Cell Reservoirs for HIV
By Jeffrey Laurence, M.D.
HIV particles assembling on the surface of an infected macrophage © 2006 Public Library of Science.For many years the CD4+ T cell (T cell for short) has been the primary focus of research concerning the immune system and HIV/AIDS. But the T cell has a close relation in our armamentarium of immune defenses, and that cell, the macrophage, is being re-examined by scientists for its potential role in maintaining hidden reservoirs for HIV infection.
Working at the University of Oxford, amfAR-funded researcher Quentin Sattentau and his colleague Joshua Tan emphasize that the macrophage is a major initial target of HIV infection. It also plays a primary role in the dementia and other neurologic problems that, prior to effective anti-HIV therapy, were so prominent in the clinical manifestations of AIDS. Macrophages possess a unique internal structure known as the virus-containing compartment (VCC), which Sattentau and Tan believe acts to maintain latent HIV reservoirs.
Writing in the August issue of Trends in Microbiology, Sattentau and Tan review several studies demonstrating that, at least in the test tube, the VCC seems to protect HIV from both internal and external attack, and acts as a place for HIV virions to assemble and be stored. VCCs can be either completely enclosed or accessible to the cell’s surface. The latter form facilitates transmission of the virus to T cells and appears to offer a unique mechanism of release. The authors suggest that new research being conducted by other amfAR-funded scientists studying tetherin, a normal cell protein that appears to prevent HIV from escaping from infected T cells, can be applied to block this transmission process because tetherin has also been shown to play a role in retaining HIV virions in VCCs.
The authors conclude by surmising that this macrophage “niche may well provide the perfect balance between optimal onward transmission [of HIV] and a safe haven,” for the virus. And they call for further study of VCCs in patients rather than just test tube models as VCCs present a possible new avenue of attack against HIV reservoirs for scientists to explore.
Dr. Laurence is amfAR’s senior scientific consultant.