title: The human immunodeficiency virus type 1 Vpr protein upregulates PVR via activation of the ATR-mediated DNA damage response pathway.
abstract: Viral infection may induce the cell-surface expression of PVR (CD155) that, upon recognition by its cognate activating DNAM-1 receptor present on cytotoxic lymphocytes, may promote antiviral immune responses. Here we show that expression of the human immunodeficiency virus type 1 (HIV-1) Vpr protein in Jurkat T cells increases cell-surface and total PVR levels. Analysis of mutated Vpr variants indicated that Vpr uses the same protein surfaces, and hence probably the same mechanisms, to upregulate PVR and arrest the cell cycle in the G2 phase. Moreover, we found that PVR upregulation by Vpr relied on the ability of the protein to activate the ATR kinase that triggers the DNA damage response pathway and G2 arrest. Finally, we showed that Vpr contributes to PVR up-modulation in HIV-infected CD4(+) T lymphocytes and inhibits the PVR downregulating activity of the viral Nef protein.
authors.affiliation: Laboratory of Immunoinfectivology, Bambino Gesù Children's Hospital, IRCCS, 00165, Rome, Italy.
authors.forename: Lia
authors.initials: L
authors.lastname: Vassena
authors.affiliation: Laboratory of Immunoinfectivology, Bambino Gesù Children's Hospital, IRCCS, 00165, Rome, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Giuliani
authors.affiliation: Laboratory of Immunoinfectivology, Bambino Gesù Children's Hospital, IRCCS, 00165, Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Matusali
authors.affiliation: Laboratory of Human Retrovirology, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada.
authors.forename: Éric A
authors.initials: ÉA
authors.lastname: Cohen
authors.affiliation: Laboratory of Immunoinfectivology, Bambino Gesù Children's Hospital, IRCCS, 00165, Rome, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Doria
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D004249:DNA Damage / Q000187:drug effects*; D016195:G2 Phase / Q000187:drug effects; D015658:HIV Infections / Q000821:virology; D015497:HIV-1; D006801:Humans; D019169:Jurkat Cells; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D011991:Receptors, Virus; C066100:poliovirus receptor; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
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