Current Biology
Volume 9, Issue 12, 17 June 1999, Pages 622-631
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Research Paper
Cell-surface expression of CD4 reduces HIV-1 infectivity by blocking Env incorporation in a Nef- and Vpu-inhibitable manner

https://doi.org/10.1016/S0960-9822(99)80284-XGet rights and content
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Abstract

Background: Human immunodeficiency virus-1 (HIV-1) infection decreases the cell-surface expression of its cellular receptor, CD4, through the combined actions of Nef, Env and Vpu. Such functional convergence strongly suggests that CD4 downregulation is critical for optimal viral replication, yet the significance of this phenomenon has so far remained a puzzle.

Results: We show that high levels of CD4 on the surface of HIV-infected cells induce a dramatic reduction in the infectivity of released virions by the sequestering of the viral envelope by CD4. CD4 is able to accumulate in viral particles while at the same time blocking incorporation of Env into the virion. Nef and Vpu, through their ability to downregulate CD4, counteract this effect.

Conclusions: The CD4-mediated ‘envelope interference’ described here probably explains the plurality of mechanisms developed by HIV to downregulate the cell-surface expression of its receptor.

Cited by (0)

J Lama, La Jolla Institute for Allergy and Immunology, Molecular Immunology Division, 10355 Science Center Drive, San Diego, California 92121, USA.

A Mangasarian and D Trono, Department of Genetics and Microbiology, CMU, 9 Avenue de Champel, CH-1211 Geneva 4, Switzerland.

E-mail address for D Trono (corresponding author): [email protected]

J.L and A.M contributed equally to this work