Engagement of CD43 enhances human immunodeficiency virus type 1 transcriptional activity and virus production that is induced upon TCR/CD3 stimulation.
Human immunodeficiency virus type 1 (HIV-1) transcriptional activity is regulated by several cytokines and T cell activators. CD43 (sialophorin) is a sialoglycoprotein expressed on the surface of a wide variety of blood cells including T lymphocytes. Several studies have shown that CD43 ligation induces proliferation and activation of human T lymphocytes. We were thus interested in defining whether CD43-mediated signaling events can modulate the life cycle of HIV-1. We demonstrate here that CD43 cross-linking potentiates HIV-1 promoter-driven activity and virus production that is seen following the engagement of the T-cell receptor (TCR).CD3 complex. This effect is independent of the CD28 co-stimulatory molecule and is mediated by both NF-kappaB and NFAT transcription factors. A number of signal transducers known to be involved in the TCR/CD3-dependent signal transduction pathway, including p56(lck), p36(lat), and SLP-76, as well as capacitative entry of calcium, are crucial for the noticed CD43 co-stimulatory effect. Calcium mobilization studies indicate that a synergy is occurring between CD43- and TCR/CD3-mediated signaling events leading to an augmented calcium release. These data suggest that CD43 can be seen as a co-stimulatory cell surface constituent that can modulate HIV-1 expression in T lymphocytes.
Barat
Corinne
C
Centre de Recherche en Infectiologie, Hôpital CHUL, Centre Hospitalier Universitaire de Québec, and Département de Biologie Médicale, Faculté de Médecine, Université Laval, Ste-Foy, Québec G1V 4G2, Canada.
Tremblay
Michel J
MJ
D015703:Antigens, CD; D018106:CD28 Antigens / Q000096:biosynthesis; D017252:CD3 Complex / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005822:Genetic Vectors; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D051917:Leukosialin; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011485:Protein Binding; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D015703:Antigens, CD; D018106:CD28 Antigens; D017252:CD3 Complex; D004268:DNA-Binding Proteins; D051917:Leukosialin; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; C465014:SPN protein, human; D012795:Sialoglycoproteins; D014157:Transcription Factors; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D002118:Calcium