The Frequency of Cytidine Editing of Viral DNA Is Differentially Influenced by Vpx and Nucleosides during HIV-1 or SIVMAC Infection of Dendritic Cells

Abstract

Two cellular factors are currently known to modulate lentiviral infection specifically in myeloid cells: SAMHD1 and APOBEC3A (A3A). SAMHD1 is a deoxynucleoside triphosphohydrolase that interferes with viral infection mostly by limiting the intracellular concentrations of dNTPs, while A3A is a cytidine deaminase that has been described to edit incoming vDNA. The restrictive phenotype of myeloid cells can be alleviated through the direct degradation of SAMHD1 by the HIV-2/SIVSM Vpx protein or else, at least in the case of HIV-1, by the exogenous supplementation of nucleosides that artificially overcome the catabolic activity of SAMHD1 on dNTPs. Here, we have used Vpx and dNs to explore the relationship existing between vDNA cytidine deamination and SAMHD1 during HIV-1 or SIVMAC infection of primary dendritic cells. Our results reveal an interesting inverse correlation between conditions that promote efficient infection of DCs and the extent of vDNA editing that may reflect the different susceptibility of vDNA to cytoplasmic effectors during the infection of myeloid cells.

HIV-1 and HIV-2 exhibit divergent interactions with HLTF and UNG2 DNA repair proteins

“…Although HIV-1 does not counteract SAMHD1 directly, it was proposed to bypass the SAMHD1-imposed restriction as a result of a more efficient reverse transcriptase that can synthesize viral cDNA in a low-dNTP environment (16). The failure of the aforementioned viral countermeasures flags HIV cDNA for processing by DNA repair enzymes, which, if not successfully completed in a low-dNTP environment set up by SAMHD1, could lead to the initiation of an innate response to viral nucleic acids, increased HIV-1 mutation rate, and/or inhibition of HIV-1 infection (17)(18)(19).…”