HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection

Marie A. Vodicka, Deanna M. Koepp, Pamela A. Silver, Michael Emerman

Research output: Contribution to journalArticle

277 Scopus citations

Abstract

HIV-1 Vpr promotes nuclear entry of viral nucleic acids in nondividing macrophages and also causes a G2 cell-cycle arrest. Consistent with its role in nuclear transport, we show Vpr localizes to the nuclear envelope in both human and yeast cells. Like the importin-β subunit of the nuclear import receptor, Vpr also interacts with the yeast importin-α subunit and nucleoporins. Moreover, overexpression of either Vpr or importin-β in yeast blocks nuclear transport of mRNAs. A mutant form of Vpr (Vpr F34I) that does not localize at the nuclear envelope, or bind to importin-α and nucleoporins, renders HIV-1 incapable of infecting macrophages efficiently. Vpr F34I, however, still causes a G2 arrest, demonstrating that the dual functions of Vpr are genetically separable. Our data suggest Vpr functionally resembles importin-β in nuclear import of the HIV-1 pre-integration complex and this function is essential for the role of Vpr in macrophage infection, but not G2 arrest.

Original languageEnglish (US)
Pages (from-to)175-185
Number of pages11
JournalGenes and Development
Volume12
Issue number2
DOIs
StatePublished - Jan 15 1998

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Keywords

  • HIV
  • Importin-β
  • Lentivirus
  • Nuclear envelope
  • Vpr

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