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The antiviral factor APOBEC3G improves CTL recognition of cultured HIV-infected T cells.
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- Additional Information
- Source:
Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE
- Publication Information:
Original Publication: New York, NY : Rockefeller University Press
- Subject Terms:
Adaptive Immunity*;
CD8-Positive T-Lymphocytes/
*immunology ;
Cytidine Deaminase/
*immunology ;
HIV Infections/
*immunology ;
HIV-1/
*immunology ;
Lymphocyte Activation/
*immunology;
APOBEC-3G Deaminase ;
Animals ;
Antigens, Viral/
genetics ;
Antigens, Viral/
immunology ;
Antigens, Viral/
metabolism ;
CD8-Positive T-Lymphocytes/
enzymology ;
CD8-Positive T-Lymphocytes/
virology ;
Cells, Cultured ;
Codon, Terminator/
genetics ;
Codon, Terminator/
immunology ;
Codon, Terminator/
metabolism ;
Cytidine Deaminase/
genetics ;
Cytidine Deaminase/
metabolism ;
Gene Deletion ;
Genes, vif/
genetics ;
Genes, vif/
immunology ;
HIV Infections/
enzymology ;
HIV Infections/
genetics ;
HIV-1/
genetics ;
HIV-1/
metabolism ;
Humans ;
Lymphocyte Activation/
genetics ;
Mice ;
Mice, Transgenic ;
Mutation ;
Proviruses/
genetics ;
Proviruses/
immunology ;
Proviruses/
metabolism ;
RNA Editing/
genetics ;
RNA Editing/
immunology ;
RNA, Viral/
genetics ;
RNA, Viral/
immunology ;
RNA, Viral/
metabolism ;
Virus Replication/
genetics ;
Virus Replication/
immunology ;
vif Gene Products, Human Immunodeficiency Virus/
genetics ;
vif Gene Products, Human Immunodeficiency Virus/
immunology - Abstract:
The cytidine deaminase APOBEC3G (A3G) enzyme exerts an intrinsic anti-human immunodeficiency virus (HIV) defense by introducing lethal G-to-A hypermutations in the viral genome. The HIV-1 viral infectivity factor (Vif) protein triggers degradation of A3G and counteracts this antiviral effect. The impact of A3G on the adaptive cellular immune response has not been characterized. We examined whether A3G-edited defective viruses, which are known to express truncated or misfolded viral proteins, activate HIV-1-specific (HS) CD8+ cytotoxic T lymphocytes (CTLs). To this end, we compared the immunogenicity of cells infected with wild-type or Vif-deleted viruses in the presence or absence of the cytidine deaminase. The inhibitory effect of A3G on HIV replication was associated with a strong activation of cocultivated HS-CTLs. CTL activation was particularly marked with Vif-deleted HIV and with viruses harboring A3G. Enzymatically inactive A3G mutants failed to enhance CTL activation. We also engineered proviruses bearing premature stop codons in their genome as scars of A3G editing. These viruses were not infectious but potently activated HS-CTLs. Therefore, the pool of defective viruses generated by A3G represents an underestimated source of viral antigens. Our results reveal a novel function for A3G, acting not only as an intrinsic antiviral factor but also as an inducer of the adaptive immune system.
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- Accession Number:
0 (Antigens, Viral)
0 (Codon, Terminator)
0 (RNA, Viral)
0 (vif Gene Products, Human Immunodeficiency Virus)
0 (vif protein, Human immunodeficiency virus 1)
EC 3.5.4.5 (APOBEC-3G Deaminase)
EC 3.5.4.5 (APOBEC3G protein, human)
EC 3.5.4.5 (Cytidine Deaminase)
- Publication Date:
Date Created: 20091230 Date Completed: 20100217 Latest Revision: 20211020
- Publication Date:
20231215
- Accession Number:
PMC2812543
- Accession Number:
10.1084/jem.20091933
- Accession Number:
20038599
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