Down-modulation of TCR/CD3 surface complexes after HIV-1 infection is associated with differential expression of the viral regulatory genes

Karen E. Willard-Gallo*, Manohar Furtado, Arséne Burny, Steven M. Wolinsky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

We have investigated the mechanism(s) involved in progressive abrogation of CD3-γ 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/CD3hi, TCR/CD3lo, 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-γ gene transcripts and TCR/CD3 surface density are down-modulated.

Original languageEnglish (US)
Pages (from-to)969-979
Number of pages11
JournalEuropean Journal of Immunology
Volume31
Issue number4
DOIs
StatePublished - 2001

Keywords

  • CD3-γ
  • HIV
  • TCR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Down-modulation of TCR/CD3 surface complexes after HIV-1 infection is associated with differential expression of the viral regulatory genes'. Together they form a unique fingerprint.

Cite this