CD4 is Retained in the Endoplasmic Reticulum by the Human Immunodeficiency Virus Type 1 Glycoprotein Precursor
Overview
Authors
Affiliations
We analyzed coexpression of the human immunodeficiency virus type 1 glycoprotein precursor, gp160, and its cellular receptor CD4 in HeLa cells to determine whether the two molecules can interact prior to transport to the cell surface. Results of studies employing coprecipitation, analysis of oligosaccharide processing, and immunocytochemistry showed that newly synthesized CD4 and gp160 form a complex prior to transport from the endoplasmic reticulum (ER). CD4 expressed by itself was transported efficiently from the ER to the cell surface, but the complex of CD4 and gp160 was retained in the ER. This retention of CD4 within the ER is probably a consequence of the very inefficient transport of gp160 itself (R. L. Willey, J. S. Bonifacino, B. J. Potts, M. A. Martin, and R. D. Klausner, Proc. Natl. Acad. Sci. USA 85:9580-9584, 1988). Retention of CD4 in the ER by gp160 may partially explain the down regulation of CD4 in human immunodeficiency virus type 1-infected T cells. Inhibition of CD4 transport appears to be a consequence of the interaction of two membrane-bound molecules, because a complex of CD4 and gp120 (the soluble extracellular domain of gp160) was transported rapidly and efficiently from the ER.
Yero A, Shi T, Clain J, Zghidi-Abouzid O, Racine G, Costiniuk C Viruses. 2024; 16(10).
PMID: 39459942 PMC: 11512404. DOI: 10.3390/v16101609.
Role of Viral Protein U (Vpu) in HIV-1 Infection and Pathogenesis.
Khan N, Geiger J Viruses. 2021; 13(8).
PMID: 34452331 PMC: 8402909. DOI: 10.3390/v13081466.
HIV Infection and Persistence in Pulmonary Mucosal Double Negative T Cells .
Meziane O, Salahuddin S, Pham T, Farnos O, Pagliuzza A, Olivenstein R J Virol. 2020; 94(24).
PMID: 32967958 PMC: 7925170. DOI: 10.1128/JVI.01788-20.
Ren Y, Korom M, Truong R, Chan D, Huang S, Kovacs C J Virol. 2018; 92(23).
PMID: 30209173 PMC: 6232479. DOI: 10.1128/JVI.00895-18.
HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.
Li G, De Clercq E Microbiol Mol Biol Rev. 2016; 80(3):679-731.
PMID: 27357278 PMC: 4981665. DOI: 10.1128/MMBR.00065-15.