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.
Highlights
Circulating blood monocytes differentiate into macrophages and dendritic cells (DCs) in tissues, where they play instructive roles in adaptive immunity [1]
Modulation of vDNA Cytidine Editing during DCs Infection triphosphohydrolase that maintains dNTPs at concentrations that are limiting for efficient reverse transcription [5,16,17,18,19,20])
In the study presented here, we have explored whether conditions that favor the efficient infection of primary human monocyte-derived dendritic cells (DCs) by either directly removing SAMHD1, or by counteracting its action on dNTPs could modulate the extent of vDNA cytidine deamination from the pool of A3 molecules present in target cells following HIV-1 or SIVMAC infection
Summary
Circulating blood monocytes differentiate into macrophages and dendritic cells (DCs) in tissues, where they play instructive roles in adaptive immunity [1]. These properties make them appealing targets for pathogens such as primate lentiviruses that use them to spread to other cell types and to derail proper antiviral responses [2,3,4]. The infection of myeloid cells by primate lentiviruses is hindered by a strong restriction that limits vDNA accumulation during the early phases of the viral life cycle [5,6,7,8,9,10,11,12,13,14,15]. Data obtained from several laboratories indicates that SAMHD1 inhibits lentiviruses by modulating dNTPs levels, recent data suggests that this may not be the sole antiviral mechanism at play [21,22,23,24]
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