Reduced nuclear import of human immunodeficiency virus type 1 preintegration complexes in the presence of a prototypic nuclear targeting signal

Gulizia, James M.; Dempsey, Michael P.; Sharova, Natasha; Bukrinsky, Michael; Spitz, L; Goldfarb, David S.; Stevenson, Mario

doi:10.1128/jvi.68.3.2021-2025.1994

Cited by 44 publications

(22 citation statements)

References 28 publications

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“…Both linear viral DNA as well as forms of circular DNA can be detected in the nucleus of infected cells [9]. Since these circles are produced only after synthesis and transport of linear viral DNA to the nucleus they can serve as convenient markers to monitor nuclear localization of viral DNA [3,12].…”

Section: Introductionmentioning

confidence: 99%

Immunodeficiency virus cDNA synthesis in resting T lymphocytes is regulated by T cell activation signals and dendritic cells

Polacino

Pinchuk

Sidorenko

et al. 1996

J of Medical Primatology

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We explored the relationship between T cell activation signals and dendritic cells (DC) in the replication cycle of immunodeficiency viruses. First we analyzed the effect of two cell cycle inhibitors (mimosine and aphidicolin) on SIV reverse transcription, circularization, and integration in macaque resting T cells stimulated with anti-CD3 mAb at the time of infection. The formation of SIV LTR circles was blocked by the G1 inhibitor mimosine. The G1/S inhibitor aphidicolin neither affected circularization nor integration of SIV DNA. Therefore, the induction of SIV LTR circle production is likely to be mediated by signaling events normally regulating the G1 to S transition. We further characterized DC-dependent HIV-expression in human T cells. We examined the effect of ligating two novel receptors, IPO-3 and Bgp95, on DC-dependent HIV-1 expression. Activation of DCs through IPO-3 receptors, and to a lesser extent Bgp95 ligation, upregulated HIV spread in these cells. The mechanisms by which IPO-3 vs. Bgp95 increase HIV-1 levels appear to be different. In particular, IPO-3 ligation alone on T cells also increased HIV-1 levels. Activation of T cells via defined surface receptors or with DCs is required for establishing HIV/SIV cDNA synthesis in T cells.

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Section: Introductionmentioning

confidence: 99%

Immunodeficiency virus cDNA synthesis in resting T lymphocytes is regulated by T cell activation signals and dendritic cells

Polacino

Pinchuk

Sidorenko

et al. 1996

J of Medical Primatology

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“…The mechanisms involved in the nuclear transport of these nucleoprotein complexes have been investigated. An active transport mechanism that requires ATP but does not depend on cell division allows the HIV-1 nucleoprotein complexes to be transported from the cytoplasm to the nucleus (4,5,20). The nuclear targeting of the HIV-1 complex is dependent on the viral matrix and Vpr proteins, while the murine leukemia virus complex requires the dissolution of the nuclear envelope during mitosis (5,20,21,27).…”

mentioning

confidence: 99%

“…An active transport mechanism that requires ATP but does not depend on cell division allows the HIV-1 nucleoprotein complexes to be transported from the cytoplasm to the nucleus (4,5,20). The nuclear targeting of the HIV-1 complex is dependent on the viral matrix and Vpr proteins, while the murine leukemia virus complex requires the dissolution of the nuclear envelope during mitosis (5,20,21,27). The viral protein composition of the nucleoprotein complexes appears to vary, depending on the isolation procedures used with HIV-1 (1,6,15,21).…”

mentioning

confidence: 99%

Concerted integration of retrovirus-like DNA by human immunodeficiency virus type 1 integrase

Goodarzi

Brackmann

et al. 1995

J Virol

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The integration of linear retrovirus DNA by the viral integrase (IN) into the host chromosome occurs by a concerted mechanism (full-site reaction). IN purified from avian myeloblastosis virus and using retrovirus-like DNA restriction fragments (487 bp in length) as donors and circular DNA (pGEM-3) as the target can efficiently catalyze that reaction. Nonionic detergent lysates of purified human immunodeficiency virus type 1 (HIV-1) virions were also capable of catalyzing the concerted integration reaction. The donor substrates were restriction fragments (469 bp) containing either U3-U5 (H-2 donor) or U5-U5 (H-5 donor) long terminal repeat sequences at their ends. As was shown previously with bacterially expressed HIV-1 IN, the U5 terminus of H-2 was preferred over the U3 terminus by virion-associated IN. The reactions involving two donors per circular target by HIV-1 IN preferred Mg 2؉ over Mn 2؉ . Both metal ions were equally effective for the circular half-site reaction involving only one donor molecule. The linear 3.8-kbp recombinant products produced from two donor insertions into pGEM were genetically selected, and the donor-target junctions of individual recombinants were sequenced. A total of 55% of the 87 sequenced recombinants had host site duplications of between 5 and 7 bp, with the HIV-1 5-bp-specific duplication predominating. The other recombinants that migrated at the linear 3.8-kbp position were mainly small deletions that were grouped into four sets of 17, 27, 40, and 47 bp, each having a periodicity mimicking a turn of the DNA helix. Aprotic solvents (dimethyl sulfoxide and 1,4-dioxane) enhanced both the half-site and the linear 3.8-kbp strand transfer reactions which favored low-salt conditions (30 mM NaCl). The order of addition of the donor and target during preincubation with HIV-1 IN on ice did not affect the quantity of linear 3.8-kbp recombinants relative to that of the circular half-site products that were produced; only the quantity of donor-donor versus donor-target recombinants was affected. The presence of Mg 2؉ in the preincubation mixtures containing donor and target substrates was not necessary for the stability of preintegration complexes on ice or at 22؇C. Comparisons of the avian and HIV-1 concerted integration reactions are discussed.

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“…In both cases, microinjected VirD2 accumulated in cell nuclei, as determined by confocal microscopy. The nuclear uptake of VirD2 was specifically inhibited by an excess of free VirD2 NLS peptide, probably due to competition for the nuclear import machinery (Guilizia et al, 1994). VirD2 nuclear import was also inhibited by coinjection of GTPyS, a nonhydrolyzable GTP analog known to block the GTPase Ran, which is absolutely essential for the transport of proteins through the nuclear pore (reviewed in Goldfarb, 1994).…”

Section: Vird2 and Vire2 Nlss Represent Two Functional Types Of Plantmentioning

confidence: 99%

Agrobacterium-Plant Cell DNA Transport: Have Virulence Proteins, Will Travel

Sheng¹,

Citovsky²

1996

The Plant Cell

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Reduced nuclear import of human immunodeficiency virus type 1 preintegration complexes in the presence of a prototypic nuclear targeting signal

Cited by 44 publications

References 28 publications

Immunodeficiency virus cDNA synthesis in resting T lymphocytes is regulated by T cell activation signals and dendritic cells

Immunodeficiency virus cDNA synthesis in resting T lymphocytes is regulated by T cell activation signals and dendritic cells

Concerted integration of retrovirus-like DNA by human immunodeficiency virus type 1 integrase

Agrobacterium-Plant Cell DNA Transport: Have Virulence Proteins, Will Travel

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