E-102 Exosomes from retrovirus infected cells carry distinct viral noncoding RNAs and proteins that control the fate of the recipient cell

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Abstract

Recently, much interest has developed regarding mechanisms of extracellular delivery of nucleic acids and proteins among virally infected and recipient cells. While the role of exosomes in viral pathogenesis and disease states remains largely unknown, it is now widely accepted that exosomes play important roles in intercellular communication, inflammation, antigen presentation, apoptosis, and pathogenesis. We have previously reported that HIV-1 encodes its own noncoding RNA that regulates viral and host gene expression. We have recently found the presence of TAR RNA in exosomes from supernatants of HIV-1 infected cells and patient sera. We report that prior exposure of naïve cells to exosomes from infected cells increased susceptibility of the recipient cells to HIV-1 infection. TAR RNA in the serum exosomes of HAART-treated patients or LTNPs also showed 10^3 copies per milliliter. TAR is able to activate cytokines in recipient cells by increasing the nuclear accumulation of p65 and p50, related to a newly formed IKKb complex in TAR treated cells which may be the result of TLR3, 7 and 8 activation. Using PCR, we have found a second class of viral RNAs termed “TAR/Gag” which, similar to TAR, does not translate into protein but acts as noncoding RNA. This RNA is complexed with SWI/SNF components potentially regulating HIV-1 latency in infected cells. The levels of both TAR and TAR/Gag increase in cART treated cells, indicating that viral suppression by anti-retroviral drugs will result in increased exosome release from infected cells containing viral noncoding RNAs and viral proteins. Therefore, exosomes from HIV-1 infected cART treated cells may contribute to the long lasting cytokine and immune activation observed in AIDS patients.

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