Document Type

Journal Article

Publication Date

7-2013

Journal

Journal of Biological Chemistry

Volume

Volume 288, Issue 27

Inclusive Pages

20014-20033

Keywords

Acquired Immunodeficiency Syndrome--metabolism; Exosomes--metabolism; HIV-1--metabolism; HIV-1--pathogenicity; RNA, Viral--metabolism

Abstract

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, first reported by us and later by others using deep sequencing, is the trans-activation response element (TAR) miRNA. In this study, we 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. We detected the host miRNA machinery proteins Dicer and Drosha in exosomes from infected cells. We report that transport of TAR RNA from the nucleus into exosomes is a CRM1 (chromosome region maintenance 1)-dependent active process. Prior exposure of naive 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. We found 104–106 copies/ml TAR RNA in exosomes derived from infected culture supernatants and 103 copies/ml TAR RNA in the serum exosomes of highly active antiretroviral therapy-treated patients or long term nonprogressors. Taken together, our 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.

Comments

This research was originally published in Journal of Biological Chemistry. Aarthi Narayanan, Sergey Iordanskiy, Ravi Das, Rachel Van Duyne, Steven Santos, et al. Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA. Journal of Biological Chemistry. 2013; 288:20014-20033. © the American Society for Biochemistry and Molecular Biology.

Peer Reviewed

1

Open Access

1

Share

COinS