The human immunodeficiency virus type 1 Vpr protein upregulates PVR via activation of the ATR-mediated DNA damage response pathway

Lia Vassena, Erica Giuliani, Giulia Matusali, Éric A. Cohen, Margherita Doria

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2664-2669
Number of pages6
JournalJournal of General Virology
Volume94
Issue numberPART 12
DOIs
Publication statusPublished - Dec 2013

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DNA Damage
HIV-1
Up-Regulation
nef Gene Products
T-Lymphocytes
Jurkat Cells
G2 Phase
Viral Proteins
Virus Diseases
Cell Cycle Checkpoints
Antiviral Agents
Membrane Proteins
Phosphotransferases
Down-Regulation
HIV
Lymphocytes
Proteins
Human immunodeficiency virus 1 vpr protein

ASJC Scopus subject areas

  • Virology

Cite this

The human immunodeficiency virus type 1 Vpr protein upregulates PVR via activation of the ATR-mediated DNA damage response pathway. / Vassena, Lia; Giuliani, Erica; Matusali, Giulia; Cohen, Éric A.; Doria, Margherita.

In: Journal of General Virology, Vol. 94, No. PART 12, 12.2013, p. 2664-2669.

Research output: Contribution to journalArticle

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