Novel role of host protein SLC25A42 in the HIV‐1 reactivation of latent HIV‐1 provirus

Abstract

AbstractDespite the effectiveness of combination antiretroviral therapy, human immunodeficiency virus (HIV) infection remains incurable. To seek new strategies to overcome HIV type 1 (HIV‐1) latency, one of the major barriers to HIV elimination, it is crucial to better understand how this state is maintained. Here, by means of an RNA interference screen employing an HIV‐1 latency model using monocytic cell lines, we identified solute carrier family 25 member 42 (SLC25A42) as a potential host factor not previously known to affect HIV‐1 latency. SLC25A42 knockdown resulted in increased HIV‐1 expression, whereas forced expression of exogenous SLC25A42 suppressed it in SLC25A42‐depleted cells. SLC25A42 depletion increased HIV‐1 proviral transcriptional elongation but did not cause HIV‐1 activation in an HIV‐1 Tat‐depleted latency model. This suggests that the role of SLC25A42 in HIV‐1 transcription depends on HIV‐1 Tat. Chromatin immunoprecipitation‐qPCR analysis further revealed that SLC25A42 accumulated on or near the HIV‐1 5ʹ long terminal repeat promoter region of the HIV‐1 provirus, suggesting a possible role in regulating HIV‐1 Tat near this promoter region. These results indicate that SLC25A42 plays a novel role in HIV‐1 latency maintenance in monocytic HIV‐1 reservoirs.