APOBEC3G upregulation by alpha interferon restricts human immunodeficiency virus type 1 infection in human peripheral plasmacytoid dendritic cells

J Gen Virol. 2008 Mar;89(Pt 3):722-730. doi: 10.1099/vir.0.83530-0.


APOBEC3G (A3G), a member of cytidine deaminase family, has potent anti-human immunodeficiency virus type 1 (HIV-1) activity. It has been demonstrated that alpha interferon (IFN-alpha) can significantly enhance the expression of A3G in human primary resting CD4(+) T-cells, macrophages and primary hepatocytes, subsequently decreasing their viral susceptibility. Plasmacytoid dendritic cells (pDCs) are key effectors in innate host immunity, mediating adaptive immune responses and stimulating IFN-alpha production in reaction to various stimuli. In this report, we demonstrate that IFN-alpha, either exogenously added to- or endogenously secreted by pDCs, can enhance the expression of A3G and its family members such as A3A, A3C and A3F. We have also shown that IFN-alpha can inhibit HIV-1 expression in pDCs. This inhibitory effect could be countered by addition of an A3G-specific short interfering RNA, indicating that IFN-alpha-induced A3G plays a key role in mediating pDCs response to HIV-1. Given the central role played by pDCs in orchestrating the IFN-alpha/A3G intercellular network and intracellular signal pathway, our data indicate that pDCs themselves are also protected by an IFN-alpha/A3G-mediated innate immunity barrier from HIV-1 infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • APOBEC-3G Deaminase
  • Antiviral Agents / immunology
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology*
  • Cells, Cultured
  • Cytidine Deaminase / metabolism*
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • Humans
  • Interferon-alpha / immunology
  • Interferon-alpha / metabolism
  • Interferon-alpha / pharmacology*
  • Up-Regulation*


  • Antiviral Agents
  • Interferon-alpha
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human
  • Cytidine Deaminase