Year: 2017
Type: article
Abstract: HIV-1 infection causes AIDS, infecting millions worldwide.The virus can persist in a state of chronic infection due to its ability to become latent.We have previously shown a link between HIV-1 infection and exosome production.Specifically, we have reported that exosomes transport viral proteins and RNA from infected cells to neighboring uninfected cells.These viral products could then elicit an innate immune response, leading to activation of the Toll-like receptor and NF-B pathways.In this study, we asked whether exosomes from uninfected cells could activate latent HIV-1 in infected cells.We observed that irrespective of combination antiretroviral therapy, both short-and long-length viral transcripts were increased in wildtype HIV-1-infected cells exposed to purified exosomes from uninfected cells.A search for a possible mechanism for this finding revealed that the exosomes increase RNA polymerase II loading onto the HIV-1 promoter in the infected cells.These viral transcripts, which include trans-activation response (TAR) RNA and a novel RNA that we termed TAR-gag, can then be packaged into exosomes and potentially be exported to neighboring uninfected cells, leading to increased cellular activation.To better decipher the exosome release pathways involved, we used siRNA to suppress expression of ESCRT (endosomal sorting complex required for transport) proteins and found that ESCRT II and IV significantly control exosome release.Collectively, these results imply that exosomes from uninfected cells activate latent HIV-1 in infected cells and that true transcrip-tional latency may not be possible in vivo, especially in the presence of combination antiretroviral therapy.
Source: Journal of Biological Chemistry
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Funders: Australian Centre for HIV and Hepatitis Virology Research, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: HIV-1 TAR derived miRNA: Implications for Latency and Pathogenesis, Nanotrap particle-based assay to quantify HIV-1 in latently-infected T cells, HIV neuropathogenesis related to exosomes containing HIV non-coding RNAs, G3418878615, HIV-1 Inhibition Using Tat peptide derivatives, A radiation-induced cellular stress activates HIV and induces killing of infected cells, G592158972, G667479965, G7102465762, G8540389298, G9000081039, G9000201836
OpenAlex ID: W2617145180