[Mechanisms of reduction of CD4 receptor expression on the surface of HIV-1 infected cells].
Specific interactions between the cell surface CD4 receptor and the HIV-1 envelope glycoprotein gp120 are responsible for the entry of HIV into host cells. Following infection, a down-modulation of CD4 at the cell surface is commonly observed. This may render cells resistant to subsequent infection by HIV as well as other viruses that also use CD4 as a portal of entry. This phenomenon is termed retroviral interference. CD4 down-modulation is complex and involves at least 3 viral gene products which include the envelope precursor gp160 and 2 auxilliary proteins Nef and Vpu. CD4 down-modulation has been observed in each of primary CD4+ T-lymphocytes and monocyte-derived macrophages, as well as both T and monocytic cell lines. CD4 down-regulation may occur at different levels. Specific binding of soluble gp120 may lead to internalization of CD4. The HIV-1 nef gene product which is expressed prior to HIV-1 structural proteins also causes the internalization of CD4 followed by its lysosomal degradation. During the late phase of viral gene expression i.e. viral structural protein synthesis, CD4-gp160 complexes forming in the ER represent another important factor leading to CD4 down-modulation. Finally, CD4 which is retained by gp160 in the ER, is specifically degraded in the presence of Vpu. Thus, it appears that CD4 down-regulation is of central importance to the life cycle of HIV-1.
Geleziunas
R
R
Centre SIDA de l'Université McGill, Montréal, Québec, Canada.
Morin
N
N
Wainberg
M A
MA
D000818:Animals; D015704:CD4 Antigens / Q000737:chemistry / Q000235:genetics*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D005786:Gene Expression Regulation; D015693:Gene Products, nef / Q000378:metabolism; D015754:Genes, nef / Q000235:genetics; D016338:Genes, vpu / Q000235:genetics; D019302:HIV Envelope Protein gp160 / Q000737:chemistry / Q000378:metabolism; D015658:HIV Infections; D015497:HIV-1; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus; D000086082:Viroporin Proteins
D015704:CD4 Antigens; D015693:Gene Products, nef; D019302:HIV Envelope Protein gp160; D054298:Human Immunodeficiency Virus Proteins; D011505:Protein-Tyrosine Kinases; D054334:Viral Regulatory and Accessory Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins
Mécanismes de réduction de l'expression des récepteurs CD4 à la surface des cellules infectées par le VIH-1.