Disease relevance of APOBEC3F

• Indeed, the mutation spectra and expression profile found for APOBEC3F indicate that this enzyme, together with APOBEC3G, accounts for the G to A hypermutation of proviruses described in HIV-infected individuals [1].
• Three of them, APOBEC3G, APOBEC3F, and APOBEC3B, block replication of human immunodeficiency virus type 1 (HIV-1) and many other retroviruses [2].
• In opposition to APOBEC genes, HIV-1 and SIV contain a virion infectivity factor (Vif) that targets APOBEC3F and APOBEC3G for polyubiquitylation and proteasomal degradation [2].
• A second human antiretroviral factor, APOBEC3F, is suppressed by the HIV-1 and HIV-2 Vif proteins [3].
• G-->A hypermutation conforming to expected APOBEC3G polynucleotide sequence preferences was inferred in 9.4% (n = 12) of the HIV-1 sequences, with a further 2.4% (n = 3) conforming to APOBEC3F, and was independently associated with reduced pretreatment viremia (reduction of 0.7 log(10) copies/ml; P = 0.001) [4].

High impact information on APOBEC3F

• Surprisingly, APOBEC3F and APOBEC3G are extensively coexpressed in nonpermissive human cells, including primary lymphocytes and the cell line CEM, where they form heterodimers [3].
• Viral RNA and low-level DNA produced in the presence of APOBEC3F or rat APOBEC1 occasionally displayed mutations, but the majority of clones were wild-type [5].
• Here, we have biochemically characterized human APOBEC3F and APOBEC3G protein complexes as a function of the HIV-1 life cycle [6].
• The mechanism of L1 inhibition did not correlate with an obvious subcellular protein distribution as APOBEC3B appeared predominantly nuclear and APOBEC3F was mostly cytosolic [7].
• A particularly high level of APOBEC3F protein in human testes and an inverse correlation between L1 activity and APOBEC3 gene number suggest the relevance of this mechanism to mammals [7].

Chemical compound and disease context of APOBEC3F

• APOBEC3G (A3G) and related cytidine deaminases, such as APOBEC3F (A3F), are potent inhibitors of retroviruses [8].
• Deoxycytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) (members of the apolipoprotein B mRNA-editing catalytic polypeptide 3 family) have RNA-binding motifs, invade assembling human immunodeficiency virus (HIV-1), and hypermutate reverse transcripts [9].
• Human APOBEC3F and APOBEC3G are double-domained deaminases that can catalyze dC-->dU deamination in HIV-1 and MLV retroviral DNA replication intermediates, targeting T-C or C-C dinucleotides, respectively [10].

Biological context of APOBEC3F

• Second, cDNA strand-specific C --> T hypermutations were not detected among L1 elements that had replicated in the presence of APOBEC3B or APOBEC3F [7].
• Members of this family (APOBEC3G and APOBEC3F) have been recently shown to be able to restrict HIV-1 replication in physiologically relevant target cells (macrophages, lymphocytes), presumably by triggering extensive deamination of the viral RNA/DNA replication intermediates [11].
• This unique genetic system further enabled us to show that expression of APOBEC3G or its homolog APOBEC3F was able to inhibit the mobility of the retrotransposon Ty1 by a mechanism that involves the deamination of cDNA cytosines [12].
• Biochemical differentiation of APOBEC3F and APOBEC3G proteins associated with HIV-1 life cycle [6].
• Here, we report an APOBEC3F-like, double deaminase domain protein from three artiodactyls: cattle, pigs and sheep [13].

Anatomical context of APOBEC3F

• APOBEC3F and APOBEC3G mRNA levels do not correlate with human immunodeficiency virus type 1 plasma viremia or CD4+ T-cell count [14].
• Like their human counterparts, APOBEC3F and APOBEC3G, the artiodactyl APOBEC3F proteins are DNA cytosine deaminases that locate predominantly to the cytosol and can inhibit the replication of HIV-1 and MLV [13].

Associations of APOBEC3F with chemical compounds

• Here, we show that only the C-terminal cytosine deaminase domain of APOBEC3F and -3G governs retroviral hypermutation [15].
• We have exploited the fact that APOBEC3C, whilst highly homologous to the C-terminal domain of APOBEC3F, exhibits a distinct target site specificity (preferring Y-C dinucleotides) in order to identify residues in APOBEC3F that might affect its target site specificity [10].

Other interactions of APOBEC3F

• Like APOBEC3G, human APOBEC3F preferentially restricts vif-deficient virus [1].
• When expressed in the yeast Saccharomyces cerevisiae, human APOBEC3C, APOBEC3F, or APOBEC3G or mouse APOBEC3 potently inhibit replication of the Ty1 LTR retrotransposon [16].
• Further, the N-terminal half determined RNase sensitivity and was necessary for the high molecular mass complex assembly of APOBEC3G but not APOBEC3F [6].

References