Modulation of CD3-gamma gene expression after HIV type 1 infection of the WE17/10 T cell line is progressive and occurs in concert with decreased production of viral p24 antigen.
HIV-1 infection of WE17/10, an IL-2-dependent CD4+ human T cell line, abrogates T cell receptor (TCR)/CD3 expression due to a transcription level defect in the CD3-gamma chain gene. Kinetic examination of surface receptor density reveals that these complexes are progressively reduced early after HIV-1 infection as the cells transition from TCR/CD3hi-->TCR/CD3lo-->TCR/CD3-. The passage from TCR/CD3hi reversible TCR/CD3lo is characterized by a steady decrease in receptor density from 100 to 50% of control values with similar kinetic for all of the viral variants tested. This first phase in TCR/CD3 downmodulation was found to occur in concert with a decrease in viral p24 antigen production. The switch from TCR/CD3- is distinguished by the conversion of individual cells to the receptor negative phenotype. Although broad kinetic differences in this second phase were observed between viral variants, its onset was consistently accompanied by a further reduction in virus production. In some of the HIV-1-infected WE17/10 cell lines, surface receptor expression was spontaneously upregulated during the second phase of infection, reversing the progression from TCR/CD3(-)-->TCR/CD3lo-->TCR/CD3hi. Thus, in HIV-1-infected WE17/10 cells, changes in CD3-gamma gene transcription are accompanied by altered viral p24 antigen production and the resulting modulation of surface receptor expression can be summarized by the formula: TCR/CD3hi reversible TCR/CD3lo reversible TCR/CD3-.
Willard-Gallo
K E
KE
International Institute of Cellular and Molecular Pathology (ICP), Brussels, Belgium.
Delmelle-Wibaut
C
C
Segura-Zapata
I
I
Janssens
M
M
Willems
L
L
Kettmann
R
R
D002460:Cell Line; D017353:Gene Deletion; D015870:Gene Expression; D015967:Gene Expression Regulation, Viral; D016655:HIV Core Protein p24 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D014158:Transcription, Genetic; D015854:Up-Regulation
D016655:HIV Core Protein p24; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta