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M94A3326.TXT
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1994-10-25
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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).