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 RIS Download
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