In-depth analysis of the interaction of HIV-1 with cellular microRNA biogenesis and effector mechanisms

Adam W. Whisnant, Hal P. Bogerd, Omar Flores, Phong Ho, Jason G. Powers, Natalias Sharova, Mario Stevenson, Chin Ho Chen, Bryan R. Cullena

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

The question of how HIV-1 interfaces with cellular microRNA (miRNA) biogenesis and effector mechanisms has been highly controversial. Here, we first used deep sequencing of small RNAs present in two different infected cell lines (TZM-bl and C8166) and two types of primary human cells (CD4+ peripheral blood mononuclear cells [PBMCs] and macrophages) to unequivocally demonstrate that HIV-1 does not encode any viral miRNAs. Perhaps surprisingly, we also observed that infection of T cells by HIV-1 has only a modest effect on the expression of cellular miRNAs at early times after infection. Comprehensive analysis of miRNA binding to the HIV-1 genome using the photoactivatable ribonucleoside-induced cross-linking and immunoprecipitation (PAR-CLIP) technique revealed several binding sites for cellular miRNAs, a subset of which were shown to be capable of mediating miRNA-mediated repression of gene expression. However, the main finding from this analysis is that HIV-1 transcripts are largely refractory to miRNA binding, most probably due to extensive viral RNA secondary structure. Together, these data demonstrate that HIV-1 neither encodes viral miRNAs nor strongly influences cellular miRNA expression, at least early after infection, and imply that HIV-1 transcripts have evolved to avoid inhibition by preexisting cellular miRNAs by adopting extensive RNA secondary structures that occlude most potential miRNA binding sites.

Original languageEnglish (US)
Article numbere00193-13
JournalmBio
Volume4
Issue number2
DOIs
StatePublished - Mar 2013

ASJC Scopus subject areas

  • Microbiology
  • Virology

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    Whisnant, A. W., Bogerd, H. P., Flores, O., Ho, P., Powers, J. G., Sharova, N., Stevenson, M., Chen, C. H., & Cullena, B. R. (2013). In-depth analysis of the interaction of HIV-1 with cellular microRNA biogenesis and effector mechanisms. mBio, 4(2), [e00193-13]. https://doi.org/10.1128/mBio.00193-13