title: HIV infection--induced posttranslational modification of T cell signaling molecules associated with disease progression.
abstract: In attempt to elucidate the mechanism of the HIV infection induced T cell unresponsiveness, we studied signal-transducing molecules proximal to the T cell receptor (TCR) in T lymphocytes of HIV-infected individuals. Total amounts of protein tyrosine kinases (PTKs) Lck, Fyn, and ZAP-70 and the zeta chain of the TCR were found significantly decreased in T cells of symptomatic/AIDS patients as well as in T cells of individuals in acute and early asymptomatic stages of HIV infection. Unexpectedly, the detection of Lck, Fyn, and ZAP-70 was reversed after the treatment of cell lysates with dithiothreitol. This suggests that PTKs Lck, Fyn, and ZAP-70 were modified by a mechanism altering the status of sulfhydryl groups. Moreover, this mechanism seems to affect selectively T cells of HIV infected patients since B cell PTKs Syk and Lyn were detected structurally and functionally intact. Interestingly, similar alterations of signaling molecules were not detected in T cells of HIV-infected long-term asymptomatic individuals. Modification of T cell PTKs may thus underlie the HIV-induced impairment of lymphocyte function and may potentially predict disease progression.
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. IStefanova@pop.niaid.nih.gov
authors.forename: I
authors.initials: I
authors.lastname: Stefanová
authors.forename: M W
authors.initials: MW
authors.lastname: Saville
authors.forename: C
authors.initials: C
authors.lastname: Peters
authors.forename: F R
authors.initials: FR
authors.lastname: Cleghorn
authors.forename: D
authors.initials: D
authors.lastname: Schwartz
authors.forename: D J
authors.initials: DJ
authors.lastname: Venzon
authors.forename: K J
authors.initials: KJ
authors.lastname: Weinhold
authors.forename: N
authors.initials: N
authors.lastname: Jack
authors.forename: C
authors.initials: C
authors.lastname: Bartholomew
authors.forename: W A
authors.initials: WA
authors.lastname: Blattner
authors.forename: R
authors.initials: R
authors.lastname: Yarchoan
authors.forename: J B
authors.initials: JB
authors.lastname: Bolen
authors.forename: I D
authors.initials: ID
authors.lastname: Horak
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D015151:Immunoblotting; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000276:immunology; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology*; D051746:ZAP-70 Protein-Tyrosine Kinase; D019061:src-Family Kinases / Q000032:analysis / Q000276:immunology
chemical_list: D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013438:Sulfhydryl Compounds; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D019061:src-Family Kinases