Production of HIV particles is regulated by altering sub-cellular localization and dynamics of Rev induced by double-strand RNA binding protein

PLoS One. 2011 Feb 22;6(2):e16686. doi: 10.1371/journal.pone.0016686.

Abstract

Human immunodeficiency virus (HIV)-1 encoded Rev is essential for export from the nucleus to the cytoplasm, of unspliced and singly spliced transcripts coding for structural and nonstructural viral proteins. This process is spatially and temporally coordinated resulting from the interactions between cellular and viral proteins. Here we examined the effects of the sub-cellular localization and dynamics of Rev on the efficiency of nucleocytoplasmic transport of HIV-1 Gag transcripts and virus particle production. Using confocal microscopy and fluorescence recovery after bleaching (FRAP), we report that NF90ctv, a cellular protein involved in Rev function, alters both the sub-cellular localization and dynamics of Rev in vivo, which drastically affects the accumulation of the viral protein p24. The CRM1-dependent nuclear export of Gag mRNA linked to the Rev Response Element (RRE) is dependent on specific domains of the NF90ctv protein. Taken together, our results demonstrate that the appropriate intracellular localization and dynamics of Rev could regulate Gag assembly and HIV-1 replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Fluorescence Recovery After Photobleaching
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Green Fluorescent Proteins / physiology
  • HIV Infections / metabolism
  • HIV Infections / virology*
  • HIV-1 / metabolism*
  • HIV-1 / physiology*
  • HeLa Cells
  • Humans
  • Nuclear Factor 90 Proteins / chemistry
  • Nuclear Factor 90 Proteins / genetics
  • Nuclear Factor 90 Proteins / metabolism
  • Nuclear Factor 90 Proteins / physiology*
  • Protein Structure, Tertiary / genetics
  • Protein Structure, Tertiary / physiology
  • Protein Transport / physiology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / physiology
  • Tissue Distribution
  • Virion / metabolism
  • Virion / physiology
  • Virus Assembly / physiology
  • Virus Replication / genetics
  • Virus Replication / physiology
  • rev Gene Products, Human Immunodeficiency Virus / genetics
  • rev Gene Products, Human Immunodeficiency Virus / metabolism*
  • rev Gene Products, Human Immunodeficiency Virus / physiology

Substances

  • Nuclear Factor 90 Proteins
  • Recombinant Fusion Proteins
  • rev Gene Products, Human Immunodeficiency Virus
  • rev protein, Human Immunodeficiency Virus-1
  • Green Fluorescent Proteins