Human immunodeficiency virus Tat associates with a specific set of cellular RNAs

Retrovirology. 2014 Jul 3;11:53. doi: 10.1186/1742-4690-11-53.

Abstract

Background: Human Immunodeficiency Virus 1 (HIV-1) exhibits a wide range of interactions with the host cell but whether viral proteins interact with cellular RNA is not clear. A candidate interacting factor is the trans-activator of transcription (Tat) protein. Tat is required for expression of virus genes but activates transcription through an unusual mechanism; binding to an RNA stem-loop, the transactivation response element (TAR), with the host elongation factor P-TEFb. HIV-1 Tat has also been shown to alter the expression of host genes during infection, contributing to viral pathogenesis but, whether Tat also interacts with cellular RNAs is unknown.

Results: Using RNA immunoprecipitation coupled with microarray analysis, we have discovered that HIV-1 Tat is associated with a specific set of human mRNAs in T cells. mRNAs bound by Tat share a stem-loop structural element and encode proteins with common biological roles. In contrast, we do not find evidence that Tat associates with microRNAs or the RNA-induced silencing complex (RISC). The interaction of Tat with cellular RNA requires an intact RNA binding domain and Tat RNA binding is linked to an increase in RNA abundance in cell lines and during infection of primary CD4+ T cells by HIV.

Conclusions: We conclude that Tat interacts with a specific set of human mRNAs in T cells, many of which show changes in abundance in response to Tat and HIV infection. This work uncovers a previously unrecognised interaction between HIV and its host that may contribute to viral alteration of the host cellular environment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • CD4-Positive T-Lymphocytes / virology
  • Cell Line
  • Gene Expression Regulation, Viral
  • HEK293 Cells
  • HIV Infections / virology*
  • HIV-1 / genetics*
  • Humans
  • MicroRNAs / genetics
  • Molecular Sequence Data
  • Protein Binding / genetics
  • RNA, Messenger / genetics*
  • RNA-Binding Proteins / genetics
  • Transcription, Genetic
  • Transcriptional Activation / genetics
  • tat Gene Products, Human Immunodeficiency Virus / genetics*

Substances

  • MicroRNAs
  • RNA, Messenger
  • RNA-Binding Proteins
  • tat Gene Products, Human Immunodeficiency Virus