Human immunodeficiency virus type 1 Vpr protein does not modulate surface expression of the CD4 receptor.
The CD4 receptor is required for the entry of human immunodeficiency virus (HIV) into target cells. It has long been known that Nef, Env, and Vpu participate in the removal of the viral receptor from the cell surface. Recently, it has been proposed that the HIV type 1 (HIV-1) Vpr protein may also play a role in the downmodulation of CD4 from the surfaces of infected cells (L. Conti, B. Varano, M. C. Gauzzi, P. Matarrese, M. Federico, W. Malorani, F. Belardelli, and S. Gessani, J. Virol. 74:10207-10211, 2000). To investigate the possible role of Vpr in the downregulation of the viral receptor Vpr alleles from HIV-1 and simian immunodeficiency virus were transiently expressed in transformed T cells and in 293T fibroblasts, and their ability to modulate surface CD4 was evaluated. All Vpr alleles efficiently arrested cells in the G(2) stage of the cell cycle. However, none of the tested Vpr proteins altered the expression of CD4 on the cell surface. In comparison, HIV-1 Nef efficiently downmodulated surface CD4 in all the experimental settings. Transformed T cells and primary lymphocytes were challenged with wild-type, Nef-defective, and Vpr-defective viruses. A significant reduction in the HIV-induced downmodulation of surface CD4 was observed in viruses lacking Nef. However, Vpr-deletion-containing viruses showed no defect in their ability to remove CD4 from the surfaces of infected cells. Our results indicate that Vpr does not play a role in the HIV-induced downmodulation of the CD4 receptor.
Argañaraz
Enrique
E
Department of Medicine. UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093-0665, USA.
Cortés
María José
MJ
Leibel
Sydney
S
Lama
Juan
J
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D002461:Cell Line, Transformed; D015536:Down-Regulation; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes; D054325:vpr Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus