In a presentation today at AIDS 2022, the twenty fourth International AIDS Conference in Montreal, scientists with the National Institute of Allergy and Infectious Diseases’ (NIAID) Vaccine Research Center (VRC) and their collaborators described how their use of cutting-edge technology revealed latest insights into cellular reservoirs of HIV and what those observations could mean for the subsequent steps in HIV cure research. NIAID is an element of the National Institutes of Health.

An enhanced understanding of the HIV-infected, memory CD4+ T cells that persist over many years in individuals taking antiretroviral therapy has been a long-time goal of HIV cure researchers. Nonetheless, technology limitations have made it difficult to isolate or analyze these individual cells of their natural state. Because of this, scientists have been unable to find out whether the cells possess distinctive attributes that HIV-cure-directed therapies may exploit.

Within the presentation, Eli Boritz, M.D., Ph.D., chief of the Virus Persistence and Dynamics Section within the VRC Laboratory of Immunology, described NIAID’s long-standing collaboration with a bioengineering research group on the University of California, San Francisco. The researchers developed a custom microfluidic sorting technology termed Focused Interrogation of Cells by Nucleic Acid Detection and Sequencing (FIND-Seq). This technology defines gene expression patterns from rare cells harboring latent HIV by generating hundreds of thousands of single-cell response containers in the shape of water-in-oil emulsions, through which messenger RNA capture and virus DNA detection could be performed sequentially while maintaining segregation amongst cells. The scientists applied the FIND-Seq technology to blood cells from six individuals with HIV who had begun taking ART while chronically infected and who had experienced a couple of 12 months of viral suppression. Using data produced by FIND-Seq, the scientists compared the gene expression patterns of HIV-infected memory CD4+ T cells to those of HIV-uninfected memory CD4+ T cells in the identical individuals.

The researchers found clear differences between the HIV-infected CD4+ T cells and their uninfected counterparts, including gene expression patterns linked to the suppression of multiple steps within the HIV lifecycle and to cell survival and proliferation. In keeping with the scientists, these results indicate that the HIV-infected memory CD4+ T-cell reservoir is a particular cell population that could be uniquely at risk of specific targeted therapies. On this regard, the study reinforces recent interest amongst scientists in improving upon HIV cure strategies which might be based on latency reversal by incorporating drugs that relieve blocks at multiple HIV lifecycle steps, and by combining these with agents that potentiate physiologic cell death.

Source:

National Institutes of Health