In a presentation today at AIDS 2022, the 24th International AIDS Conference in Montreal, scientists from the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID) and their colleagues ยท contributors described how their use of cutting-edge technology revealed new insights into the cellular reservoirs of HIV and what these observations could mean for the next steps in HIV cure research. NIAID is part of the National Institutes of Health.
A better understanding of HIV-infected memory CD4+ T cells that persist for decades in individuals taking antiretroviral therapy has long been a goal of HIV care researchers. However, technological limitations have made it difficult to isolate or analyze these individual cells in their natural state. As a result, scientists have been unable to determine whether the cells possess distinctive attributes that therapies aimed at curing HIV can exploit.
In the presentation, Eli Boritz, MD, Ph.D., chief of the Viral Dynamics and Persistence Section of the VRC Laboratory of Immunology, described NIAID’s long-standing collaboration with a bioengineering research group of the University of California, San Francisco. The researchers developed a custom microfluidic sorting technology called focused interrogation of cells by nucleic acid detection and sequencing (FIND-Seq). This technology defines gene expression patterns of rare cells harboring latent HIV by generating millions of single-cell reaction vessels in the form of water-in-oil emulsions, in which messenger RNA capture and detection of ‘DNA of the virus can be made sequentially while maintaining segregation between cells. . The scientists applied FIND-Seq technology to blood cells from six people with HIV who had started taking ART while chronically infected and who had experienced more than a year of viral suppression. Using the data produced by FIND-Seq, the scientists compared the gene expression patterns of HIV-infected memory CD4+ T cells with those of HIV-uninfected memory CD4+ T cells in the same individuals .
The researchers found clear differences between HIV-infected CD4+ T cells and their uninfected counterparts, including gene expression patterns linked to the suppression of multiple steps in the HIV life cycle and to cell survival and proliferation cellular According to the scientists, these results indicate that the HIV-infected memory CD4+ T cell pool is a distinct cell population that may be uniquely susceptible to specific targeted therapies. In this regard, the study reinforces the recent interest among scientists to improve HIV treatment strategies that rely on the reversal of latency by incorporating drugs that relieve blocks at multiple stages of the HIV life cycle and combining them with agents that enhance physiological cell death.
Source:
National Institutes of Health