Document 3326
 DOCN  M94A3326
 TI    Peptidase activity of CD26 is not necessary for its function in HIV
       entry and cytopathic effect.
 DT    9412
 AU    Callebaut C; Krust B; Marie I; Jacotot E; Robert N; Guichard G; Briand
       JP; Muller S; Barth A; Montagnier L; et al; Unite de Virologie &
       Immunologie Cellulaire, Institut Pasteur,; Paris, France.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):101 (abstract no. PA0022). Unique
       Identifier : AIDSLINE ICA10/94369249
 AB    CD26, also known as dipeptidyl peptidase IV (DPP IV), serves as a
       coreceptor of CD4 for entry of HIV into permissive cells. In the
       infected cell, CD26 is involved along CD4 in the mechanism of the
       characteristic cytopathic effect (CPE) of HIV which is triggered by the
       membrane expressed HIV envelope glycoproteins. CD26 is a serine
       peptidase manifesting substrate specifity for dipeptide motifs which
       interestingly are conserved in the V3 loops of HIV-1, HIV-2 and SIV
       isolates. However, cleavage of gp120 does not occur when bound to cells
       permissive to HIV or when incubated with enzyme preparations manifesting
       high levels of DPP IV activity; thus suggesting that the catalytic
       activity of CD26 may not be necessary for its function in HIV infection.
       In accord with this, a modified peptide referred to as MP-A2 which at 10
       microM suppresses the DPP IV activity by more than 95% has no effect on
       HIV infection. On the other hand, another modified peptide MP-J1 at 5-20
       microM suppresses HIV entry without affecting the DPP IV activity of
       CD26. MP-J1 when added after HIV entry, inhibits the development of CPE
       without any significant effect on the production of HIV. The IC50 values
       of MP-J1 for the inhibition of HIV entry and CPE are 5 and 50 microM,
       respectively. These observations suggest the presence of a gp120 binding
       site in the CD26 molecule independent of the catalytic site which is
       responsible for the peptidase activity. Therefore, CD26 may serve as a
       coreceptor by recognizing the conserved motifs in the V3 loop without
       actually cleaving its target.
 DE    Animal  Antigens, Differentiation, T-Lymphocyte/*PHYSIOLOGY  Binding
       Sites  Cytopathogenic Effect, Viral/PHYSIOLOGY  Dipeptidyl
       Peptidases/ANTAGONISTS & INHIB/*PHYSIOLOGY  Human  HIV/DRUG
       EFFECTS/*PHYSIOLOGY/*PATHOGENICITY  HIV Envelope Protein
       gp120/PHYSIOLOGY  HIV Infections/ETIOLOGY  HIV-2/PHYSIOLOGY  In Vitro
       Peptide Fragments/PHYSIOLOGY  Peptides/PHARMACOLOGY  Receptors,
       HIV/PHYSIOLOGY  SIV/PHYSIOLOGY  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).