SIVSM/HIV-2 Vpx proteins promote retroviral escape from a proteasome-dependent restriction pathway present in human dendritic cells.
BACKGROUND
Vpx is a non-structural protein coded by members of the SIVSM/HIV-2 lineage that is believed to have originated by duplication of the common vpr gene present in primate lentiviruses. Vpx is incorporated into virion particles and is thus present during the early steps of viral infection, where it is thought to drive nuclear import of viral nucleoprotein complexes. We have previously shown that Vpx is required for SIVMAC-derived lentiviral vectors (LVs) infection of human monocyte-derived dendritic cells (DCs). However, since the requirement for Vpx is specific for DCs and not for other non-dividing cell types, this suggests that Vpx may play a role other than nuclear import.


RESULTS
Here, we show that the function of Vpx in the infection of DCs is conserved exclusively within the SIVSM/HIV-2 lineage. At a molecular level, Vpx acts by promoting the accumulation of full length viral DNA. Furthermore, when supplied in target cells prior to infection, Vpx exerts a similar effect following infection of DCs with retroviruses as divergent as primate and feline lentiviruses and gammaretroviruses. Lastly, the effect of Vpx overlaps with that of the proteasome inhibitor MG132 in DCs.


CONCLUSIONS
Overall, our results support the notion that Vpx modifies the intracellular milieu of target DCs to facilitate lentiviral infection. The data suggest that this is achieved by promoting viral escape from a proteasome-dependent pathway especially detrimental to viral infection in DCs.
Goujon
Caroline
C
LaboRetro, INSERM U758, Ecole Normale Supérieure de Lyon, IFR 128 BioSciences Lyon-Gerland, Lyon-Biopole, France. cgoujon@ens-lyon.fr <cgoujon@ens-lyon.fr>
Rivière
Lise
L
Jarrosson-Wuilleme
Loraine
L
Bernaud
Jeanine
J
Rigal
Dominique
D
Darlix
Jean-Luc
JL
Cimarelli
Andrea
A
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004279:DNA, Viral / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000821:virology*; D015498:HIV-2 / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D007700:Kinetics; D009000:Monocytes / Q000166:cytology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000378:metabolism / Q000472:pathogenicity*; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*
D004279:DNA, Viral; C074286:VPX protein, Human immunodeficiency virus 2; C513059:VPX protein, Simian immunodeficiency virus; D054334:Viral Regulatory and Accessory Proteins; D046988:Proteasome Endopeptidase Complex