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.
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.
Cucchiarini
M
M
Laboratoire de Virologie, Faculté de Médecine, Nice, France.
Cagnon
L
L
Giordanengo
V
V
Doglio
A
A
Lefebvre
J C
JC
D001483:Base Sequence; D015153:Blotting, Western; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers / Q000737:chemistry; D015536:Down-Regulation / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D015686:Gene Products, env / Q000378:metabolism*; D015693:Gene Products, nef / Q000235:genetics / Q000502:physiology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015498:HIV-2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000502:physiology; D014779:Virus Replication; D054299:env Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; D000086082:Viroporin Proteins
D015704:CD4 Antigens; D017931:DNA Primers; D015686:Gene Products, env; D015693:Gene Products, nef; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D054298:Human Immunodeficiency Virus Proteins; D011498:Protein Precursors; D054334:Viral Regulatory and Accessory Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C066315:gp140 envelope protein, Human immunodeficiency virus 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins