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Cellular microRNA and P bodies modulate host-HIV-1 interactions.

MicroRNAs (miRNAs), approximately 22 nt noncoding RNAs, assemble into RNA-induced silencing complexes (RISCs) and localize to cytoplasmic substructures called P bodies. Dictated by base-pair complementarity between miRNA and a target mRNA, miRNAs specifically repress posttranscriptional expression of several mRNAs. Here we report that HIV-1 mRNA interacts with RISC proteins and that disrupting P body structures enhances viral production and infectivity. In HIV-1-infected human T lymphocytes, we identified a highly abundant miRNA, miR-29a, which specifically targets the HIV-1 3'UTR region. Inhibiting miR-29a enhanced HIV-1 viral production and infectivity, whereas expressing a miR-29 mimic suppressed viral replication. We also found that specific miR-29a-HIV-1 mRNA interactions enhance viral mRNA association with RISC and P body proteins. Thus we provide an example of a single host miRNA regulating HIV-1 production and infectivity. These studies highlight the significance of miRNAs and P bodies in modulating host cell interactions with HIV-1 and possibly other viruses.

Pubmed ID: 19560422

Authors

  • Nathans R
  • Chu CY
  • Serquina AK
  • Lu CC
  • Cao H
  • Rana TM

Journal

Molecular cell

Publication Data

June 26, 2009

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01 AI043198
  • Agency: NIAID NIH HHS, Id: R01 AI043198-11
  • Agency: NIAID NIH HHS, Id: R56 AI041404
  • Agency: NIAID NIH HHS, Id: R56 AI041404-12A1

Mesh Terms

  • Base Sequence
  • Binding Sites
  • Cytoplasmic Structures
  • DEAD-box RNA Helicases
  • HIV-1
  • Humans
  • MicroRNAs
  • Molecular Sequence Data
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RNA, Viral
  • RNA-Induced Silencing Complex
  • Ribonuclease III
  • T-Lymphocytes
  • Virus Replication