Robert Siliciano's laboratory identified the latent reservoir for HIV in resting CD4+ T cells. This reservoir is the major barrier to curing HIV infection and is the focus of an intense international research effort in which Dr. Siliciano's lab plays a key role.
Analysis of Non-Induced HIV Proviruses
Latent HIV genomes in resting CD4+ T cells represent the major barrier to curing the infection with antiretroviral therapy. Detection of these latent viruses in patients is done with a viral outgrowth assay in which resting cells are activated to release replication competent virus. Polymerase chain reaction (PCR) is also used to quantitate this latent reservoir. However, PCR assays detect 300-fold more infected cells than the culture assays do, presumably because many of the proviruses detected by PCR are defective. As efforts to target the latent reservoir progress, the need for a reliable assay for latent infection is becoming an urgent research priority.
A previous EXROP student made considerable progress on this project last summer, showing that methylation of a CpG island in the HIV promoter was not responsible for the failure of the many cells containing proviruses to give rise to replication competent virus. The analysis of these non-induced proviruses is continuing on many fronts and would make an excellent summer project.