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Evolutionarily conserved and non-conserved retrovirus restriction activities of artiodactyl APOBEC3F proteins.

Jónsson SR, Haché G, Stenglein MD, Fahrenkrug SC, Andrésdóttir V, Harris RS - Nucleic Acids Res. (2006)

Bottom Line: Retrovirus restriction is attributable to deaminase-dependent and -independent mechanisms, as deaminase-defective mutants retain significant anti-retroviral activity.These data indicate that DNA cytosine deamination; sub-cellular localization and retrovirus restriction activities are conserved in mammals, whereas active site location, local mutational preferences and Vif susceptibility are not.Together, these studies indicate that some properties of the mammal-specific, APOBEC3-dependent retroelement restriction system are necessary and conserved, but others are simultaneously modular and highly adaptable.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.

ABSTRACT
The APOBEC3 proteins are unique to mammals. Many inhibit retrovirus infection through a cDNA cytosine deamination mechanism. HIV-1 neutralizes this host defense through Vif, which triggers APOBEC3 ubiquitination and degradation. Here, we report an APOBEC3F-like, double deaminase domain protein from three artiodactyls: cattle, pigs and sheep. 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. Retrovirus restriction is attributable to deaminase-dependent and -independent mechanisms, as deaminase-defective mutants retain significant anti-retroviral activity. However, unlike human APOBEC3F and APOBEC3G, the artiodactyl APOBEC3F proteins have an active N-terminal DNA cytosine deaminase domain, which elicits a broader dinucleotide deamination preference, and they are resistant to HIV-1 Vif. These data indicate that DNA cytosine deamination; sub-cellular localization and retrovirus restriction activities are conserved in mammals, whereas active site location, local mutational preferences and Vif susceptibility are not. Together, these studies indicate that some properties of the mammal-specific, APOBEC3-dependent retroelement restriction system are necessary and conserved, but others are simultaneously modular and highly adaptable.

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Related in: MedlinePlus

Artiodactyl A3F proteins are resistant to HIV-1 Vif. Parameters are identical to those used in Figure 4A, except for the inclusion of plasmids encoding HIV-1IIIB Vif (+) or a HIV-1IIIB ΔVif (−) control, which has translation stop codons at 33 and 34 amino acids (79).
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fig6: Artiodactyl A3F proteins are resistant to HIV-1 Vif. Parameters are identical to those used in Figure 4A, except for the inclusion of plasmids encoding HIV-1IIIB Vif (+) or a HIV-1IIIB ΔVif (−) control, which has translation stop codons at 33 and 34 amino acids (79).

Mentions: HsA3F, HsA3G and chimpanzee A3G are neutralized by HIV-1 Vif [e.g. (51,64)]. However, many other monkey A3G proteins (e.g. African green monkey) and MmA3 are completely resistant (27,61–63,69). The full sets of interactions that govern the A3-Vif conflict have not been determined, and the artiodactyl A3F proteins are likely to prove useful in this regard. Therefore, HIV-GFP infectivity was monitored in the presence or absence of HIV-1 Vif and human, artiodactyl or mouse A3 proteins. As described previously, expression of HIV-1 Vif neutralized HsA3F and HsA3G (although the former to a lesser extent) and caused a proportional recovery of HIV-GFP infectivity [Figure 6; e.g. (13,51,64)]. Expression of HIV-1 Vif failed to enhance the infectivity of HIV-GFP produced in the presence of MmA3 or any of the artiodactyl A3F proteins. Thus, the artiodactyl A3F proteins were fully resistant to HIV-1 Vif.


Evolutionarily conserved and non-conserved retrovirus restriction activities of artiodactyl APOBEC3F proteins.

Jónsson SR, Haché G, Stenglein MD, Fahrenkrug SC, Andrésdóttir V, Harris RS - Nucleic Acids Res. (2006)

Artiodactyl A3F proteins are resistant to HIV-1 Vif. Parameters are identical to those used in Figure 4A, except for the inclusion of plasmids encoding HIV-1IIIB Vif (+) or a HIV-1IIIB ΔVif (−) control, which has translation stop codons at 33 and 34 amino acids (79).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1636497&req=5

fig6: Artiodactyl A3F proteins are resistant to HIV-1 Vif. Parameters are identical to those used in Figure 4A, except for the inclusion of plasmids encoding HIV-1IIIB Vif (+) or a HIV-1IIIB ΔVif (−) control, which has translation stop codons at 33 and 34 amino acids (79).
Mentions: HsA3F, HsA3G and chimpanzee A3G are neutralized by HIV-1 Vif [e.g. (51,64)]. However, many other monkey A3G proteins (e.g. African green monkey) and MmA3 are completely resistant (27,61–63,69). The full sets of interactions that govern the A3-Vif conflict have not been determined, and the artiodactyl A3F proteins are likely to prove useful in this regard. Therefore, HIV-GFP infectivity was monitored in the presence or absence of HIV-1 Vif and human, artiodactyl or mouse A3 proteins. As described previously, expression of HIV-1 Vif neutralized HsA3F and HsA3G (although the former to a lesser extent) and caused a proportional recovery of HIV-GFP infectivity [Figure 6; e.g. (13,51,64)]. Expression of HIV-1 Vif failed to enhance the infectivity of HIV-GFP produced in the presence of MmA3 or any of the artiodactyl A3F proteins. Thus, the artiodactyl A3F proteins were fully resistant to HIV-1 Vif.

Bottom Line: Retrovirus restriction is attributable to deaminase-dependent and -independent mechanisms, as deaminase-defective mutants retain significant anti-retroviral activity.These data indicate that DNA cytosine deamination; sub-cellular localization and retrovirus restriction activities are conserved in mammals, whereas active site location, local mutational preferences and Vif susceptibility are not.Together, these studies indicate that some properties of the mammal-specific, APOBEC3-dependent retroelement restriction system are necessary and conserved, but others are simultaneously modular and highly adaptable.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.

ABSTRACT
The APOBEC3 proteins are unique to mammals. Many inhibit retrovirus infection through a cDNA cytosine deamination mechanism. HIV-1 neutralizes this host defense through Vif, which triggers APOBEC3 ubiquitination and degradation. Here, we report an APOBEC3F-like, double deaminase domain protein from three artiodactyls: cattle, pigs and sheep. 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. Retrovirus restriction is attributable to deaminase-dependent and -independent mechanisms, as deaminase-defective mutants retain significant anti-retroviral activity. However, unlike human APOBEC3F and APOBEC3G, the artiodactyl APOBEC3F proteins have an active N-terminal DNA cytosine deaminase domain, which elicits a broader dinucleotide deamination preference, and they are resistant to HIV-1 Vif. These data indicate that DNA cytosine deamination; sub-cellular localization and retrovirus restriction activities are conserved in mammals, whereas active site location, local mutational preferences and Vif susceptibility are not. Together, these studies indicate that some properties of the mammal-specific, APOBEC3-dependent retroelement restriction system are necessary and conserved, but others are simultaneously modular and highly adaptable.

Show MeSH
Related in: MedlinePlus