A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells

Michael I. Bukrinsky, Sheryl Haggerty, Michael P. Dempsey, Natalia Sharova, Alexei Adzhubei, Lynn Spitz, Paul Lewis, David Goldfarb, Michael Emerman, Mario Stevenson

Research output: Contribution to journalArticle

686 Citations (Scopus)

Abstract

PERMISSIVENESS of the host cell to productive infection by onco-retroviruses is cell-cycle dependent1, and nuclear localization of viral nucleoprotein preintegration complexes will occur only after cells have passed through mitosis2. In contrast, establishment of an integrated provirus after infection by the lentivirus HIV-1 is independent of host cell proliferation3-5. The ability of HIV-1 to replicate in non-dividing cells is partly accounted for by the kary-ophilic properties of the viral preintegration complex which, after virus infection, is actively transported to the host cell nucleus. Here we report that the gag matrix protein of HIV-1 contains a nuclear localization sequence which, when conjugated to a heterologous protein, directs its nuclear import. In addition, HIV-1 mutants containing amino-acid substitutions in this nuclear localization signal integrate and replicate within dividing but not growth-arrested cells, and thus display a phenotype more representative of an onco-retrovirus.

Original languageEnglish (US)
Pages (from-to)666-669
Number of pages4
JournalNature
Volume365
Issue number6447
StatePublished - 1993
Externally publishedYes

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Nuclear Localization Signals
HIV-1
Infection
Proteins
Lentivirus Infections
Retroviridae Infections
gag Gene Products
Proviruses
Nucleoproteins
Cell Nucleus Active Transport
Virus Diseases
Retroviridae
Amino Acid Substitution
Cell Nucleus
Cell Cycle
Phenotype
Growth

ASJC Scopus subject areas

  • General

Cite this

Bukrinsky, M. I., Haggerty, S., Dempsey, M. P., Sharova, N., Adzhubei, A., Spitz, L., ... Stevenson, M. (1993). A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature, 365(6447), 666-669.

A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. / Bukrinsky, Michael I.; Haggerty, Sheryl; Dempsey, Michael P.; Sharova, Natalia; Adzhubei, Alexei; Spitz, Lynn; Lewis, Paul; Goldfarb, David; Emerman, Michael; Stevenson, Mario.

In: Nature, Vol. 365, No. 6447, 1993, p. 666-669.

Research output: Contribution to journalArticle

Bukrinsky, MI, Haggerty, S, Dempsey, MP, Sharova, N, Adzhubei, A, Spitz, L, Lewis, P, Goldfarb, D, Emerman, M & Stevenson, M 1993, 'A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells', Nature, vol. 365, no. 6447, pp. 666-669.
Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubei A, Spitz L et al. A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature. 1993;365(6447):666-669.
Bukrinsky, Michael I. ; Haggerty, Sheryl ; Dempsey, Michael P. ; Sharova, Natalia ; Adzhubei, Alexei ; Spitz, Lynn ; Lewis, Paul ; Goldfarb, David ; Emerman, Michael ; Stevenson, Mario. / A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. In: Nature. 1993 ; Vol. 365, No. 6447. pp. 666-669.
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