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

Publication ,  Journal Article
Narayanan, A; Iordanskiy, S; Das, R; Van Duyne, R; Santos, S; Jaworski, E; Guendel, I; Sampey, G; Dalby, E; Iglesias-Ussel, M; Popratiloff, A ...
Published in: The Journal of biological chemistry
July 2013

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 10(4)-10(6) copies/ml TAR RNA in exosomes derived from infected culture supernatants and 10(3) 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.

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Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

July 2013

Volume

288

Issue

27

Start / End Page

20014 / 20033

Related Subject Headings

  • RNA, Viral
  • Proto-Oncogene Proteins
  • Membrane Proteins
  • Humans
  • Hela Cells
  • HeLa Cells
  • HIV-1
  • HIV Long Terminal Repeat
  • Exosomes
  • Down-Regulation
 

Citation

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Narayanan, A., Iordanskiy, S., Das, R., Van Duyne, R., Santos, S., Jaworski, E., … Kashanchi, F. (2013). Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA. The Journal of Biological Chemistry, 288(27), 20014–20033. https://doi.org/10.1074/jbc.m112.438895
Narayanan, Aarthi, Sergey Iordanskiy, Ravi Das, Rachel Van Duyne, Steven Santos, Elizabeth Jaworski, Irene Guendel, et al. “Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA.The Journal of Biological Chemistry 288, no. 27 (July 2013): 20014–33. https://doi.org/10.1074/jbc.m112.438895.
Narayanan A, Iordanskiy S, Das R, Van Duyne R, Santos S, Jaworski E, et al. Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA. The Journal of biological chemistry. 2013 Jul;288(27):20014–33.
Narayanan, Aarthi, et al. “Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA.The Journal of Biological Chemistry, vol. 288, no. 27, July 2013, pp. 20014–33. Epmc, doi:10.1074/jbc.m112.438895.
Narayanan A, Iordanskiy S, Das R, Van Duyne R, Santos S, Jaworski E, Guendel I, Sampey G, Dalby E, Iglesias-Ussel M, Popratiloff A, Hakami R, Kehn-Hall K, Young M, Subra C, Gilbert C, Bailey C, Romerio F, Kashanchi F. Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA. The Journal of biological chemistry. 2013 Jul;288(27):20014–20033.

Published In

The Journal of biological chemistry

DOI

EISSN

1083-351X

ISSN

0021-9258

Publication Date

July 2013

Volume

288

Issue

27

Start / End Page

20014 / 20033

Related Subject Headings

  • RNA, Viral
  • Proto-Oncogene Proteins
  • Membrane Proteins
  • Humans
  • Hela Cells
  • HeLa Cells
  • HIV-1
  • HIV Long Terminal Repeat
  • Exosomes
  • Down-Regulation