The Frequency of Cytidine Editing of Viral DNA Is Differentially Influenced by Vpx and Nucleosides during HIV-1 or SIVMAC Infection of Dendritic Cells.
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.
CIRI, Centre International de Recherche en Infectiologie, Lyon, F69364, France; INSERM, U1111, 46 Allée d'Italie, Lyon, F69364, France; Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, Lyon, F69364, France; CNRS, UMR5308, 46 Allée d'Italie, Lyon, F69364, France; University of Lyon, Lyon I, UMS3444/US8 BioSciences Gerland, Lyon, F69364, France.
Xuan-Nhi
XN
Nguyen
CIRI, Centre International de Recherche en Infectiologie, Lyon, F69364, France; INSERM, U1111, 46 Allée d'Italie, Lyon, F69364, France; Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, Lyon, F69364, France; CNRS, UMR5308, 46 Allée d'Italie, Lyon, F69364, France; University of Lyon, Lyon I, UMS3444/US8 BioSciences Gerland, Lyon, F69364, France.
Véronique
V
Barateau
CIRI, Centre International de Recherche en Infectiologie, Lyon, F69364, France; INSERM, U1111, 46 Allée d'Italie, Lyon, F69364, France; Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, Lyon, F69364, France; CNRS, UMR5308, 46 Allée d'Italie, Lyon, F69364, France; University of Lyon, Lyon I, UMS3444/US8 BioSciences Gerland, Lyon, F69364, France; Institute of BioMedical Science (IBMS), East China Normal University (ECNU), Shanghai, China.
Nannan
N
Wu
CIRI, Centre International de Recherche en Infectiologie, Lyon, F69364, France; INSERM, U1111, 46 Allée d'Italie, Lyon, F69364, France; Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, Lyon, F69364, France; CNRS, UMR5308, 46 Allée d'Italie, Lyon, F69364, France; University of Lyon, Lyon I, UMS3444/US8 BioSciences Gerland, Lyon, F69364, France.
Gregory
G
Berger
CIRI, Centre International de Recherche en Infectiologie, Lyon, F69364, France; INSERM, U1111, 46 Allée d'Italie, Lyon, F69364, France; Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, Lyon, F69364, France; CNRS, UMR5308, 46 Allée d'Italie, Lyon, F69364, France; University of Lyon, Lyon I, UMS3444/US8 BioSciences Gerland, Lyon, F69364, France.
Andrea
A
Cimarelli
D003562:Cytidine / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics*; D003713:Dendritic Cells / Q000187:drug effects / Q000821:virology*; D057809:HEK293 Cells; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D009705:Nucleosides / Q000494:pharmacology*; D048348:Reverse Transcription / Q000187:drug effects; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins / Q000494:pharmacology*
D004279:DNA, Viral; D009705:Nucleosides; C074286:VPX protein, Human immunodeficiency virus 2; D054334:Viral Regulatory and Accessory Proteins; D003562:Cytidine