The HIV Protease Inhibitor Nelfinavir Inhibits Kaposi's Sarcoma-associated Herpesvirus Replication in Vitro

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2011 Mar 16

PMID 21402841

Citations 44

Authors

Soren Gantt

Jacquelyn Carlsson

Minako Ikoma

Eliora Gachelet

Matthew Gray

Adam P Geballe

Lawrence Corey

Corey Casper

Michael Lagunoff

Jeffrey Vieira

Affiliations

Soon will be listed here.

Abstract

Kaposi's sarcoma (KS) is the most common HIV-associated cancer worldwide and is associated with high levels of morbidity and mortality in some regions. Antiretroviral (ARV) combination regimens have had mixed results for KS progression and resolution. Anecdotal case reports suggest that protease inhibitors (PIs) may have effects against KS that are independent of their effect on HIV infection. As such, we evaluated whether PIs or other ARVs directly inhibit replication of Kaposi's sarcoma-associated herpesvirus (KSHV), the gammaherpesvirus that causes KS. Among a broad panel of ARVs tested, only the PI nelfinavir consistently displayed potent inhibitory activity against KSHV in vitro as demonstrated by an efficient quantitative assay for infectious KSHV using a recombinant virus, rKSHV.294, which expresses the secreted alkaline phosphatase. This inhibitory activity of nelfinavir against KSHV replication was confirmed using virus derived from a second primary effusion lymphoma cell line. Nelfinavir was similarly found to inhibit in vitro replication of an alphaherpesvirus (herpes simplex virus) and a betaherpesvirus (human cytomegalovirus). No activity was observed with nelfinavir against vaccinia virus or adenovirus. Nelfinavir may provide unique benefits for the prevention or treatment of HIV-associated KS and potentially other human herpesviruses by direct inhibition of replication.

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