Inhibition of human immunodeficiency virus type 1 infection in a T-cell line (CEM) by new dipeptidyl-peptidase IV (CD26) inhibitors

J. D. Jiang, S. Wilk, J. Li, H. Zhang, J. G. Bekesi

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Phenylalanyl-pyrrolidine-2-nitrile (Phe-pyrr-2-CN) and arginyl(PMC)- pyrrolidine-2-nitrile (Arg(PMC)-pyrr-2-CN) are two dipeptidyl peptidase IV/CD26 (DPP-IV/CD26) inhibitors designed and synthesized by our group. These two compounds suppress the enzymatic activity of DPP-IV/CD26 in a competitive and reversible manner. Pretreatment of CEM cells with either of the compounds yielded a marked albeit transient reduction of HIV infection, as measured by HIV1 p24 production, RT activity and syncytium formation. The ID50 value of Phe-Pyrr-2-CN and Arg(PMC)-pyrr-2-CN in HIV1 inhibition was 5.3 μM and 2,4 μM, respectively. Administration of either of the DPP-IV/CD26 inhibitors I h after HIV1 infection did not suppress HIV1 production. An analog whose inhibitory activity toward DPP-IV/CD26 was abolished by blocking the N- terminal of Phe-pyrr-2-CN with the 9-fluorenymethyloxycarbonyl (Fmoc) group had no effect on HIV1 infection. An additive effect of HIV1 inhibition was observed in combinations of either of the DPP-IV/CD26 inhibitors with CD4 monoclonal antibody. These results suggest that DPP-IV/CD26 enzymatic activity may play a role in facilitating HIV1 infection of human CD4+ T cells at the entry process. DPP4V/CD26 inhibitors may therefore have potential use in combination with other drugs to prevent HIV1 transmission.

Original languageEnglish
Pages (from-to)255-266
Number of pages12
JournalResearch in Virology
Volume148
Issue number4
DOIs
StatePublished - 1997

Keywords

  • CEM cells
  • DPP-IV/CD26
  • Dipeptidyl-peptidase IV
  • Entry process
  • HIV
  • Nitrile inhibitors
  • T lymphocyte

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