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CD4 down-modulation during infection of human T cells with human immunodeficiency virus type 1 involves independent activities of vpu, env, and nef

Chen, Benjamin K. and Ghandi, Rajesh T. and Baltimore, David (1996) CD4 down-modulation during infection of human T cells with human immunodeficiency virus type 1 involves independent activities of vpu, env, and nef. Journal of Virology, 70 (9). pp. 6044-6053. ISSN 0022-538X.

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The human immunodeficiency virus type 1 (HIV-1) genes vpu, env, and nef have all been implicated in modulating the levels of cell surface CD4 on infected cells. To quantitatively assess the relative contribution of each gene product to the regulation of CD4 during HIV infection of Jurkat T cells and peripheral blood mononuclear cells, we have developed an infectious HIV reporter system which expresses different combinations of these genes. To distinguish infected cells in the early or late stages of infection from uninfected cells, these viruses were designed to express human placental alkaline phosphatase with the kinetics of either early or late viral genes. Flow cytometry to detect placental alkaline phosphatase and CD4 in infected cells showed that vpu, env, and nef are independently capable of down-modulation of CD4. As predicted by their respective expression patterns, nef down- modulated CD4 rapidly during the early phase of virus infection whereas vpu and env functioned late in the infection. In both Jurkat cells and peripheral blood mononuclear cells, a combination of the three genes was more efficient than any one or two genes, demonstrating that all three genes are required to achieve maximal CD4 down-modulation. In primary cells, down-modulation of CD4 was less efficient than in Jurkat cells and there was a stronger dependence on nef function for reducing cell surface CD4. HIV therefore has three genes that are able to independently down-modulate CD4; together, they can eliminate the bulk of cell surface CD4.

Item Type:Article
Baltimore, David0000-0001-8723-8190
Additional Information:Copyright © 1996 by the American Society for Microbiology. Received 11 March 1996/Accepted 20 May 1996 We are grateful to Joshy Jacob for the suggestion to use PLAP and for technical advice concerning the use of the PLAP. We thank George Cohen, Christopher Roman, and Kalle Saksela for critical reading of and helpful comments on the manuscript. B.K.C. was supported by a Medical Scientist Training Program grant.
Issue or Number:9
Record Number:CaltechAUTHORS:CHEjvir96
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2768
Deposited By: Archive Administrator
Deposited On:26 Apr 2006
Last Modified:02 Oct 2019 22:56

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