Exosomes from Uninfected Cells Cause Transcriptional Activation of Latent HIV-1 Virus in Infected Immune Cells



Barclay, Robert A

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HIV-1 infection causes AIDS, a significant problem in today’s world. It can be combatted through the use of combination antiretroviral therapy, which can lower viral load to undetectable levels. However, because HIV-1 is able to integrate its genome with the host cell’s, achieving latency, there is no effective way to target the viral reservoir. In previous studies, it has been shown that there is a link between HIV-1 and exosomes. Specifically, exosomes were shown to transport viral proteins and RNA from infected cells to neighboring uninfected cells. These viral products could then suppress the PKR pathway, leading to increased pathogenesis. In this study, exosomes from uninfected cells were observed to increase short and long-length viral transcripts within wild-type HIV-infected cells. This effect was again observed when infected cells were under cART. An investigation into a possible mechanism for this phenomenon revealed that the exosomes potentially cause an increase in RNA Polymerase II activity within the infected cells. Collectively, these results imply that exosomes from uninfected cells cause an activation of HIV-1 from latency in infected cells.



HIV, Exosomes, Latency, Transcription