Cellular APOBEC3G restricts HIV-1 infection in resting CD4+ T cells

Nature. 2005 May 5;435(7038):108-14. doi: 10.1038/nature03493. Epub 2005 Apr 13.


In contrast to activated CD4+ T cells, resting human CD4+ T cells circulating in blood are highly resistant to infection with human immunodeficiency virus (HIV). Whether the inability of HIV to infect these resting CD4+ T cells is due to the lack of a key factor, or alternatively reflects the presence of an efficient mechanism for defence against HIV, is not clear. Here we show that the anti-retroviral deoxycytidine deaminase APOBEC3G strongly protects unstimulated peripheral blood CD4+ T cells against HIV-1 infection. In activated CD4+ T cells, cytoplasmic APOBEC3G resides in an enzymatically inactive, high-molecular-mass (HMM) ribonucleoprotein complex that converts to an enzymatically active low-molecular-mass (LMM) form after treatment with RNase. In contrast, LMM APOBEC3G predominates in unstimulated CD4+ T cells, where HIV-1 replication is blocked and reverse transcription is impaired. Mitogen activation induces the recruitment of LMM APOBEC3G into the HMM complex, and this correlates with a sharp increase in permissivity for HIV infection in these stimulated cells. Notably, when APOBEC3G-specific small interfering RNAs are introduced into unstimulated CD4+ T cells, the early replication block encountered by HIV-1 is greatly relieved. Thus, LMM APOBEC3G functions as a potent post-entry restriction factor for HIV-1 in unstimulated CD4+ T cells. Surprisingly, sequencing of the reverse transcripts slowly formed in unstimulated CD4+ T cells reveals only low levels of dG dA hypermutation, raising the possibility that the APOBEC3G-restricting activity may not be strictly dependent on deoxycytidine deamination

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Retracted Publication

MeSH terms

  • APOBEC-3G Deaminase
  • Amino Acid Sequence
  • Base Sequence
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / enzymology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Cytidine Deaminase
  • Cytoplasm / enzymology
  • Enzyme Activation
  • Gene Products, vif / metabolism
  • Genes, env / genetics
  • HIV Infections / metabolism*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / growth & development
  • HIV-1 / physiology*
  • Humans
  • Lymphocyte Activation / drug effects
  • Mitogens / pharmacology
  • Molecular Sequence Data
  • Molecular Weight
  • Multiprotein Complexes / metabolism
  • Nucleoside Deaminases
  • Organ Specificity
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA Interference
  • Repressor Proteins
  • Ribonucleases / metabolism
  • Ubiquitin / metabolism
  • Virus Replication / physiology
  • vif Gene Products, Human Immunodeficiency Virus


  • Gene Products, vif
  • Mitogens
  • Multiprotein Complexes
  • Proteins
  • Repressor Proteins
  • Ubiquitin
  • vif Gene Products, Human Immunodeficiency Virus
  • Ribonucleases
  • Nucleoside Deaminases
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human
  • Cytidine Deaminase