Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA

Aarthi Narayanan, Sergey Iordanskiy, Ravi Das, Rachel Van Duyne, Steven Santos, Elizabeth Jaworski, Irene Guendel, Gavin Sampey, Elizabeth Dalby, Maria Iglesias-Ussel, Anastas Popratiloff, Ramin Hakami, Kylene Kehn-Hall, Mary Young, Caroline Subra, Caroline Gilbert, Charles Bailey, Fabio Romerio, Fatah Kashanchi

Research output: Contribution to journalArticlepeer-review

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 ofTARRNAin 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.Wedetected 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 downregulated 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 andRNAprofiles that may contribute to disease pathology in AIDS.

Original languageEnglish (US)
Pages (from-to)20014-20033
Number of pages20
JournalJournal of Biological Chemistry
Volume288
Issue number27
DOIs
StatePublished - Jul 5 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA'. Together they form a unique fingerprint.

Cite this