DNA Deamination Mediates Innate Immunity to Retroviral Infection

Abstract

The May 28, 2003 immediate early online version of this article (Cell 113, 803-809, 13 June 2003) contained one sentence that did not appear in the printed version. In the results subsection entitled "CEM15/APOBEC3G Is Incorporated into MLV Virions," a bracketed sentence appeared in the following context: The CEM15/APOBEC3G-mediated suppression of HIV infection is thought to be accomplished by protein transferred as a virion component from virus producing cells into target cells (curiously, such physical transfer of CEM15/ APOBEC3G appears uninhibitable by Vif) (Sheehy et al., 2002). The bracketed text was removed prior to publication of the definitive printed and corresponding online versions of the manuscript. It was our intention that this correction should have occurred in all versions of the article. The authors and Cell Press apologize for any inconvenience that may have been caused.

Large-scale DNA editing of retrotransposons accelerates mammalian genome evolution

“…To detect edited elements, we assumed that a newly edited element should be almost identical to its ancestral element except for a few dense clusters of G-to-A mismatches, as such clusters are the hallmark of APOBEC3 editing [10][11][12][13] . To confirm that the mismatches are due to DNA editing, we exploited the asymmetry, or strand specificity, of editing: as opposed to random mutagenesis, APOBEC3 generates C-to-U mutations specifically on the negative strand of the element (with respect to the ORF), yielding clusters of G-to-A mutations, but not C-to-T, on the positive strand [10][11][12] .…”

“…To confirm that the mismatches are due to DNA editing, we exploited the asymmetry, or strand specificity, of editing: as opposed to random mutagenesis, APOBEC3 generates C-to-U mutations specifically on the negative strand of the element (with respect to the ORF), yielding clusters of G-to-A mutations, but not C-to-T, on the positive strand [10][11][12] . We therefore aligned, pairwise, the positive strands of all retrotransposons from selected families, and scanned the alignments for windows containing a particularly large number of G-to-A mismatches but no mismatches of any other type (Fig.…”

“…Occasionally, multiple cytosine-to-uracil deaminations are introduced on the negative-strand retroviral DNA after reverse transcription by proteins of the APOBEC3 (apolipoprotein B mRNA-editing enzyme and catalytic polypeptide 3) family [10][11][12][13] . While encounter with APOBEC3 impairs some viruses, others successfully integrate into the host genome, bearing G-to-A mutations compared with their original sequence.…”

Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions

“…The molecular nature of permissivity and the exact function of Vif in infection of nonpermissive cells was not known until recently when a series of reports showed that a host cellular protein known as APOBEC3G (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G) is a potent inhibitor of HIV infection in the nonpermissive cells [70,71]. APOBEC3G is a member of the cytidine deaminase family, which prevents viral cDNA synthesis via deaminating deoxycytidines (dC) in the minus-strand retroviral cDNA replication intermediate [72][73][74][75][76]. As a result, it creates stop codons or G-A transitions in the newly synthesized viral cDNA which is then subjective to elimination by host DNA repair machinery [74,76].…”

Intracellular trafficking of retroviral vectors: obstacles and advances

“…81,82 The human APOBEC3 members act during reverse transcription by deaminating C to U in single-stranded viral cDNA, which induces guanine to adenine mutations in the complementary cDNA strand. 83 To function, human APOBEC3G is packaged into virions in producer cells but blocks viral replication in target cells (discussed in Harris and Liddament 75 ), most likely by degrading the viral cDNA between late reverse transcription and integration. 84 In defense, the lentiviruses use their viral infectivity factor (Vif) accessory protein to prevent APOBEC3 packaging into virions in producer cells and circumvent restriction in target cells (reviewed in Anderson and Hope 30 and Harris and Liddament 75 ).…”