Induction by human immunodeficiency viruses types 1 and 2 of degradation of CD4 but not of a CD4 mutant unable to bind viral envelope glycoproteins.

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

Induction by human immunodeficiency viruses types 1 and 2 of degradation of CD4 but not of a CD4 mutant unable to bind viral envelope glycoproteins.

J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Apr 15;8(5):427-36. Unique Identifier : AIDSLINE MED/95211534
Cucchiarini M; Cagnon L; Giordanengo V; Doglio A; Lefebvre JC; Laboratoire de Virologie, Faculte de Medecine, Nice, France.

Abstract: HIV-1 appears to use a multiple gene strategy to regulate CD4 receptor expression, which emphasizes the importance of this regulation in the viral life cycle. The cytoplasmic interaction between gp160 and CD4 is probably the major event governing CD4 down-regulation, although other viral proteins, such as Nef (CD4 cell surface localization) and Vpu (CD4 degradation), are thought to participate as well. Because of the lack of vpu in HIV-2, we investigated the effects of two HIV-2 isolates (ROD 10 and EHO) on CD4 expression in the CEM T-cell line. We found that these HIV-2 strains induce CD4 degradation to a similar extent as that induced by an HIV-1 isolate (BRU). To assess the role of each viral protein involved in CD4 regulation (gp, Nef and Vpu), we developed cell lines expressing a mutated form of CD4 unable to efficiently bind gp160, in addition to their endogenous CD4. Using this system, we provide evidence that the mutated CD4 is always expressed in HIV-1-, and HIV-2-infected cells, independent of the presence of Nef, while the endogenous CD4 is completely lost. These results highlight the key role of intracytoplasmic gp-CD4 interaction, explaining in vitro the CD4 down-regulation in T-cell lines.

Keywords: Antigens, CD4/GENETICS/*METABOLISM Base Sequence Blotting, Western Cell Line Down-Regulation (Physiology)/*GENETICS DNA Primers/CHEMISTRY Enzyme-Linked Immunosorbent Assay Gene Expression Regulation, Viral/GENETICS Gene Products, env/*METABOLISM Gene Products, nef/GENETICS/PHYSIOLOGY Gene Products, vpu/GENETICS/PHYSIOLOGY Human HIV Envelope Protein gp120/METABOLISM HIV-1/GENETICS/*METABOLISM/PHYSIOLOGY HIV-2/GENETICS/*METABOLISM/PHYSIOLOGY Molecular Sequence Data Mutation Polymerase Chain Reaction Protein Precursors/*METABOLISM Support, Non-U.S. Gov't Virus Replication JOURNAL ARTICLE
950730
M9570915

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1995. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1995. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .