HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase

Gallay, Philippe; Swingler, Simon; Song, Jinping; Bushman, Frederic D.; Trono, Didier

doi:10.1016/0092-8674(95)90097-7

Cited by 340 publications

(287 citation statements)

References 27 publications

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“…HIV-1 proviral constructs. The X4-tropic proviral constructs R8 and Nefdefective R8⌬N were described previously (28). R8-based chimeras R8BaL and R8AD8 express the Env genes of the R5-tropic isolates BaL and AD8.…”

Section: Methodsmentioning

confidence: 99%

Nef Stimulates Human Immunodeficiency Virus Type 1 Replication in Primary T Cells by Enhancing Virion-Associated gp120 Levels: Coreceptor-Dependent Requirement for Nef in Viral Replication

Lundquist

Zhou

Aiken

2004

J Virol

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The Nef protein enhances human immunodeficiency virus type 1 (HIV-1) replication through an unknown mechanism. We and others have previously reported that efficient HIV-1 replication in activated primary CD4 ؉ T cells depends on the ability of Nef to downregulate CD4 from the cell surface. Here we demonstrate that Nef greatly enhances the infectivity of HIV-1 particles produced in primary T cells. Nef-defective HIV-1 particles contained significantly reduced quantities of gp120 on their surface; however, Nef did not affect the levels of virion-associated gp41, indicating that Nef indirectly stabilizes the association of gp120 with gp41. Surprisingly, Nef was not required for efficient replication of viruses that use CCR5 for entry, nor did Nef influence the infectivity or gp120 content of these virions. Nef also inhibited the incorporation of CD4 into HIV-1 particles released from primary T cells. We propose that Nef, by downregulating cell surface CD4, enhances HIV-1 replication by inhibiting CD4-induced dissociation of gp120 from gp41. The preferential requirement for Nef in the replication of X4-tropic HIV-1 suggests that the ability of Nef to downregulate CD4 may be most important at later stages of disease when X4-tropic viruses emerge.

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Section: Methodsmentioning

confidence: 99%

Nef Stimulates Human Immunodeficiency Virus Type 1 Replication in Primary T Cells by Enhancing Virion-Associated gp120 Levels: Coreceptor-Dependent Requirement for Nef in Viral Replication

Lundquist

Zhou

Aiken

2004

J Virol

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“…22 Unlike retroviruses, lentiviruses are capable of transducing quiescent cells. 23 For HIV, this process appears to be facilitated by the following viral proteins: (1) the integrase protein, 24,25 (2) the matrix protein from gag, 26 (3) the accessory protein vpr 27 and (4) the central polypurine tract (cPPT). 28 As a result of their capacity to transduce nondividing cells -although for some cell types, progression through the cell cycle from G0 to G1b is necessary for efficient, complete reverse transcription of the viral genome 29 -lentiviral vector development has received much interest.…”

Section: Lentivirus-based Vectorsmentioning

confidence: 99%

Lentiviral vectors for cancer immunotherapy: transforming infectious particles into therapeutics

2007

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Lentiviral vectors have emerged as promising tools for both gene therapy and immunotherapy purposes. They exhibit several advantages over other viral systems in that they are less immunogenic and are capable of transducing a wide range of different cell types, including dendritic cells (DC). DC transduced ex vivo with a whole range of different (tumor) antigens were capable of inducing strong antigen-specific T-cell responses, both in vitro and in vivo. Recently, the administration of lentiviral vectors in vivo has gained substantial interest as an alternative method for antigenspecific immunization. This method offers a number of advantages over DC vaccines as the same lentivirus can in principle be used for all patients resulting in a significantly reduced cost and requirement for considerably less expertise for the generation and administration of lentiviral vaccines. By selectively targeting lentiviral vectors to, or restricting transgene expression in certain cell types, selectivity, safety and efficacy can be further improved. This review will focus on the use of direct administration of lentiviral vectors encoding tumor-associated antigens (TAA) for the induction of tumor-specific immune responses in vivo, with a special focus on problems related to the generation of large amounts of highly purified virus and specific targeting of antigenpresenting cells (APC).

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“…The predominant phosphoamino acids in these proteins were phosphoserine and/or phosphothreonine. Tyrosine phosphorylation of retroviral protein was recently demonstrated in HIV matrix protein (MA) [12] and it was shown that a direct interaction between tyrosine-phosphorylated MA and the central domain of the integrase governed the HIV nuclear import [13].…”

Section: Introductionmentioning

confidence: 99%

The p15 matrix protein of moloney murine leukemia virus is a phosphotyrosine protein

Seri

Priel

1996

FEBS Letters

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HIV nuclear import is governed by the phosphotyrosine-mediated binding of matrix to the core domain of integrase

Cited by 340 publications

References 27 publications

Nef Stimulates Human Immunodeficiency Virus Type 1 Replication in Primary T Cells by Enhancing Virion-Associated gp120 Levels: Coreceptor-Dependent Requirement for Nef in Viral Replication

Nef Stimulates Human Immunodeficiency Virus Type 1 Replication in Primary T Cells by Enhancing Virion-Associated gp120 Levels: Coreceptor-Dependent Requirement for Nef in Viral Replication

Lentiviral vectors for cancer immunotherapy: transforming infectious particles into therapeutics

The p15 matrix protein of moloney murine leukemia virus is a phosphotyrosine protein

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