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-beta subunit of the nuclear import receptor, Vpr also interacts with the yeast importin-alpha subunit and nucleoporins. Moreover, overexpression of either Vpr or importin-beta 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-alpha 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-beta 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.

• PMID: 9436978
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Reference Type

Journal Article | Research Support, U.S. Gov't, P.H.S.

Authors

Vodicka MA, Koepp DM, Silver PA, Emerman M

Primary Lit For

NSP1 | SRP1 | KAP95 | Importin complex, KAP60-KAP95

Additional Lit For

Review For