Analysis of non-infectious HIV particles produced in presence of HIV proteinase inhibitor

Abstract

Newly developed substrate analogue peptidomimetics are able to inhibit the human immunodeficiency virus, HIV-1 proteinase at nanomolar concentration. In HIV infected cell culture they exhibit antiviral activity. We have analyzed the non-infectious HIV particles produced in chronically HIV infected cell culture in presence of one of these inhibitors. The total production of virus particles was not substantially reduced in drug treated cultures, compared to non-inhibited control cultures, but the infectivity of these virus particles was reduced about 100 fold. The processing of gag and gag-pol protein precursor was inhibited; only borderline activity of reverse transcriptase (RT) could be detected in these particles and they contained nonprocessed gag precursor protein. Thin section electron microscopy of inhibitor-treated, HIV-infected cells revealed reduced viral cytopathogenicity and both inhibition of particle assembly and incomplete maturation of the particles formed. The HIV particles produced in the presence of the proteinase inhibitor were studded with envelope glycoprotein knobs and often comprised multiple budding regions, but were morphologically immature.