SIVSM/HIV-2 Vpx proteins promote retroviral escape from a proteasome-dependent restriction pathway present in human dendritic cells

doi:10.1186/1742-4690-4-2

Retrovirology

Volume 4

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Goujon C
Rivière L
Jarrosson-Wuilleme L
Bernaud J
Rigal D
Darlix JL
Cimarelli A

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Rivière L
Jarrosson-Wuilleme L
Bernaud J
Rigal D
Darlix JL
Cimarelli A
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Research

SIV_SM/HIV-2 Vpx proteins promote retroviral escape from a proteasome-dependent restriction pathway present in human dendritic cells

Caroline Goujon¹ , Lise Rivière¹ , Loraine Jarrosson-Wuilleme¹ , Jeanine Bernaud² , Dominique Rigal² , Jean-Luc Darlix¹ and Andrea Cimarelli¹

¹LaboRetro, INSERM U758, Ecole Normale Supérieure de Lyon, IFR 128 BioSciences Lyon-Gerland, Lyon-Biopole, France

²Etablissement Français du Sang, Lyon, France

author email corresponding author email

Retrovirology 2007, 4:2doi:10.1186/1742-4690-4-2


Published:	9 January 2007

Abstract

Background

Vpx is a non-structural protein coded by members of the SIV_SM/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 SIV_MAC-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 SIV_SM/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.

Conclusion

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.