title: Characterization of simian immunodeficiency virus SIVSM/human immunodeficiency virus type 2 Vpx function in human myeloid cells.
abstract: Human immunodeficiency virus type 2 (HIV-2)/simian immunodeficiency virus SIV(SM) Vpx is incorporated into virion particles and is thus present during the early steps of infection, when it has been reported to influence the nuclear import of viral DNA. We recently reported that Vpx promoted the accumulation of full-length viral DNA following the infection of human monocyte-derived dendritic cells (DCs). This positive effect was exerted following the infection of DCs with cognate viruses and with retroviruses as divergent as HIV-1, feline immunodeficiency virus, and even murine leukemia virus, leading us to suggest that Vpx counteracted an antiviral restriction present in DCs. Here, we show that Vpx is required, albeit to a different extent, for the infection of all myeloid but not of lymphoid cells, including monocytes, macrophages, and monocytoid THP-1 cells that had been induced to differentiate with phorbol esters. The intracellular localization of Vpx was highly heterogeneous and cell type dependent, since Vpx localized differently in HeLa cells and DCs. Despite these differences, no clear correlation between the functionality of Vpx and its intracellular localization could be drawn. As a first insight into its function, we determined that SIV(SM)/HIV-2 and SIV(RCM) Vpx proteins interact with the DCAF1 adaptor of the Cul4-based E3 ubiquitin ligase complex recently described to associate with HIV-1 Vpr and HIV-2 Vpx. However, the functionality of Vpx proteins in the infection of DCs did not strictly correlate with DCAF1 binding, and knockdown experiments failed to reveal a functional role for this association in differentiated THP-1 cells. Lastly, when transferred in the context of a replication-competent viral clone, Vpx was required for replication in DCs.
authors.affiliation: LaboRetro, Department of Human Virology, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Goujon
authors.forename: Vanessa
authors.initials: V
authors.lastname: Arfi
authors.forename: Thomas
authors.initials: T
authors.lastname: Pertel
authors.forename: Jeremy
authors.initials: J
authors.lastname: Luban
authors.forename: Julia
authors.initials: J
authors.lastname: Lienard
authors.forename: Dominique
authors.initials: D
authors.lastname: Rigal
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Darlix
authors.forename: Andrea
authors.initials: A
authors.lastname: Cimarelli
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism; D015498:HIV-2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D022423:Myeloid Cells / Q000378:metabolism*; D017354:Point Mutation / Q000235:genetics; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C074286:VPX protein, Human immunodeficiency virus 2; C513059:VPX protein, Simian immunodeficiency virus; D054334:Viral Regulatory and Accessory Proteins