Despite the positive advances that anti-human immunodeficiency virus (HIV) therapy, commonly called anti-retroviral therapy (ART) or highly active antiretroviral therapy (HAART), has had on the life expectancy of HIV-positive people, finding a cure for HIV or acquired immunodeficiency syndrome (AIDS) has remained elusive.
“One of the major challenges in curing HIV is that there is a persistent latent reservoir of virus that is not targeted by current antiretroviral treatments and is hidden from immune cells. When treatment is interrupted, this reservoir of the virus allows the HIV to rapidly rebound,” explained corresponding author Andrew J. Henderson, PhD, professor of medicine and microbiology.
In an effort to identify cellular pathways that influence the establishment, maintenance and reversal of HIV persistence, the researchers conducted studies with yeast to screen a large library of human factors for binding to HIV deoxyribonucleic acid (DNA) sequences responsible for virus’ expression. As a result, they identified several factors as potential regulators and confirmed that a subset of factors did control HIV in infected cells by increasing and decreasing levels of HIV expression.
“Our study identified novel transcription factors that influence HIV and provide an appreciation into cellular networks that influence activation and repression of different HIV strains,” said Dr. Henderson.
According to the researchers, understanding the mechanisms that control HIV expression will provide insight into HIV replication, latency and pathogenesis. “By gaining an understanding of the cellular pathways that control HIV, we might be able to target them and alter the behavior of this latent reservoir,” Dr. Henderson added.
These findings appear online in the journal PNAS.
Funding for this study was provided by the NIH, NIAID RO1 Al138960 to AJH, NIH NIGMS R35 GM128625 to JIFBand the Providence /Boston CFAR (P30A1042853) and amfAR Mathilde Krim Fellowship (109263 59 RKRL) to LMA.