Argañaraz Enrique, Cortés María José, Leibel Sydney, Lama Juan
Department of Medicine. UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093-0665, USA.
J Virol. 2002 Apr;76(8):4125-30. doi: 10.1128/jvi.76.8.4125-4130.2002.
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.
人类免疫缺陷病毒（HIV）进入靶细胞需要CD4受体。长期以来，人们已知Nef、Env和Vpu参与从细胞表面去除病毒受体。最近，有人提出1型HIV（HIV-1）的Vpr蛋白可能也在从受感染细胞表面下调CD4方面发挥作用（L. Conti、B. Varano、M. C. Gauzzi、P. Matarrese、M. Federico、W. Malorani、F. Belardelli和S. Gessani，《病毒学杂志》74:10207 - 10211，2000年）。为了研究Vpr在病毒受体下调中的可能作用，将来自HIV-1和猿猴免疫缺陷病毒的Vpr等位基因在转化的T细胞和293T成纤维细胞中瞬时表达，并评估它们调节表面CD4的能力。所有Vpr等位基因均有效地将细胞阻滞在细胞周期的G(2)期。然而，所测试的Vpr蛋白均未改变细胞表面CD4的表达。相比之下，HIV-1 Nef在所有实验条件下均有效地下调了表面CD4。用野生型、Nef缺陷型和Vpr缺陷型病毒攻击转化的T细胞和原代淋巴细胞。在缺乏Nef的病毒中，观察到HIV诱导的表面CD4下调显著减少。然而，含Vpr缺失的病毒在从受感染细胞表面去除CD4的能力方面没有缺陷。我们的结果表明，Vpr在HIV诱导的CD4受体下调中不发挥作用。
