Down-modulation of TCR/CD3 surface complexes after HIV-1 infection is associated with differential expression of the viral regulatory genes
| Autor: | K E, Willard-Gallo, M, Furtado, A, Burny, S M, Wolinsky |
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| Rok vydání: | 2001 |
| Předmět: |
Gene Expression Regulation
Viral Time Factors CD3 Complex Dose-Response Relationship Drug Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes HIV Core Protein p24 Receptors Antigen T-Cell Down-Regulation rev Gene Products Human Immunodeficiency Virus Oligonucleotides Antisense Flow Cytometry Gene Products nef Cell Line Gene Products rev Gene Products tat HIV-1 Humans RNA Viral tat Gene Products Human Immunodeficiency Virus RNA Messenger nef Gene Products Human Immunodeficiency Virus Signal Transduction |
| Zdroj: | European journal of immunology. 31(4) |
| ISSN: | 0014-2980 |
| Popis: | We have investigated the mechanism(s) involved in progressive abrogation of CD3-gamma gene expression after HIV-1 or HIV-2 infection. A comparison of intracellular virus expression with T cell receptor surface density, revealed both high and low levels of viral p24 antigen in the TCR/CD3(hi), TCR/CD3(lo), and TCR/CD3(-) cells. Furthermore, in non-productively infected cells expressing the multiply spliced, virally encoded tat, rev, and nef regulatory gene transcripts, the same progressive loss of surface TCR/CD3 complexes was observed. We treated HIV-1-infected cells with antisense (AS) phosphorothioate oligodeoxynucleotides (P-OdN) targeted to the viral regulatory genes. All of the HIV-1 sequence-specific AS-P-OdN's inhibited intracellular p24 antigen expression in a time- and dose-dependent manner; although, blocking p24 expression alone was not sufficient to modulate TCR/CD3 surface density. Only Tat-AS and Nef-AS were able to delay TCR/CD3 down-modulation on receptor-positive cells or drive receptor up-regulation on receptor-negative cells. In contrast, Rev-AS accelerated TCR/CD3 loss on receptor-positive cells. RT-PCR revealed that Tat-AS and Nef-AS reduce the level of tat, nef, and rev transcripts, while Rev-AS increases the level of tat and nef transcripts in infected cells. Thus, when intracellular conditions favor expression of tat and/or nef in the absence of rev, CD3-gamma gene transcripts and TCR/CD3 surface density are down-modulated. |
| Databáze: | OpenAIRE |
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