BESTATIN-MEDIATED INHIBITION OF LEUCINE AMINOPEPTIDASE MAY HINDER HIV-INFECTION

Bestatin, an inhibitor of leucine aminopeptidase (LAPase), significant ly decreased HIV infection as reflected by a reduced number of positiv e immunofluorescent cells, p24 levels, reverse transcriptase activity and the number of proviral copies found in Bestatin-treated cells. Cel lular and extracellular LAPase activity in infected cells was higher t han the LAPase activity found in uninfected cells. However, cellular a nd extracellular LAPase activity as well as total protein kinase C act ivity was lower in Bestatin-treated cells. Conversely, the incubation of human lymphocytic HUT78 cells with LAPase promotes HIV infectivity. The possible role of LAPase in the pathophysiology of HIV was assesse d by determining LAPase serum levels in HIV infected patients. LAPase activity levels were three orders of magnitude greater in sera obtaine d from HIV patients than those detected in sera of uninfected individu als. Although Bestatin reduced HIV infection, a moderate decrease in t he reverse transcriptase activity of chronically-infected H9 human T-l ymphocytic cells was observed. Based on the higher levels of LAPase pr esent in the serum of HIV patients and on the combined inhibitory effe ct of Bestatin on LAPase and on protein kinase C activities, we sugges t that LAPase may play an important role in the early events of HIV in fection such as viral entry. (C) 1997 Elsevier Science B.V.