title: Interruption of T-cell signal transduction by lentivirus lytic peptides from HIV-1 transmembrane protein.
abstract: Two peptide segments designated LLP1 (residues 828-855) and LLP2 (residues 768-788) of the HIV-1 transmembrane (TM) envelope protein display structural and functional properties of calmodulin (CaM) binding. These LLP segments may contribute to cytopathogenesis by binding cellular CaM and inhibiting normal CaM-regulated signal transduction pathways. To determine whether these peptides could interrupt signal transduction in vivo, a cellular assay which uses a reporter gene linked to the nuclear factor of activated T cells (NF-AT) was used. Signal transduction perturbation was tested by exogenous addition of LLPs, W-7 or ionomycin; the LLPs inhibited NF-AT-mediated signal transduction as measured by reduced reporter activity. The LLP inhibition profile of NF-AT-driven luciferase activity was similar to the CaM inhibitor W-7. This was in direct contrast to ionomycin, a mobile calcium ion carrier which caused a significant increase in luciferase activity. These findings are consistent with the hypothesis that the CaM-binding properties of TM may contribute to defects in signal transduction leading to the T-cell anergy observed in patients infected with HIV-1.
authors.affiliation: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Beary
authors.forename: S B
authors.initials: SB
authors.lastname: Tencza
authors.forename: T A
authors.initials: TA
authors.lastname: Mietzner
authors.forename: R C
authors.initials: RC
authors.lastname: Montelaro
mesh_terms: D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000378:metabolism*; D008213:Lymphocyte Activation; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell