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

Abstract

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

• Authors: Ya-Lin Chiu, Vanessa B Soros, Jason F Kreisberg, Kim Stopak, Wes Yonemoto, Warner C Greene
• Journal: Nature (Nature) Vol. 435 Issue 7038 Pg. 108-14 (May 05 2005) ISSN: 1476-4687 [Electronic] England
• PMID: 15829920 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Retracted Publication)

Chemical References

• 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

Topics

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