Exosomes are nano-sized vesicles produced by healthy and virus-infected cells. Exosomes derived from infected cells have been shown to contain viral microRNAs (miRNAs). HIV-1 encodes its own miRNAs that regulate viral and host gene expression. The most abundant HIV-1-derived miRNA is the TAR (Trans-Activation Response element) miRNA.
In this study, researchers from George Mason University demonstrate the presence of TAR RNA in exosomes from cell culture supernatants of HIV-1 infected cells and patient sera. TAR miRNA was not in Ago2 complexes outside the exosomes but enclosed within the exosomes. They detected the host miRNA machinery proteins Dicer and Drosha in exosomes from infected cells. They report that transport of TAR RNA from the nucleus into exosomes is a CRM1 (Chromosome Region Maintenance 1)-dependent active process. Prior exposure of naïve cells to exosomes from infected cells increased susceptibility of the recipient cells to HIV-1 infection. Exosomal TAR RNA down regulated apoptosis by lowering Bim and Cdk9 proteins in recipient cells. They found 104 -106 copies/ml of TAR RNA in exosomes derived from infected culture supernatants and 103 copies/ml of TAR RNA in the serum exosomes of Highly active antiretroviral therapy (HAART)-treated patients or Long term nonprogressors (LTNPs). Taken together, these experiments demonstrated that HIV-1 infected cells produced exosomes that are uniquely characterized by their proteomic and RNA profiles that may contribute to disease pathology in AIDS.
- Narayanan A, Iordanskiy S, Das R, Van Duyne R, Santos S, Jaworski E, Guendel I, Sampey G, Gerhart E, Iglesias-Ussel M, Popratiloff A, Hakami R, Kehn-Hall K, Young M, Subra C, Gilbert C, Bailey C, Romerio F, Kashanchi F. (2013) Exosomes derived from HIV-1 infected cells contain TAR RNA. J Biol Chem [Epub ahead of print]. [article]