Interruption of T‐cell signal transduction by lentivirus lytic peptides from HIV‐1 transmembrane protein

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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.