The HIV Protease Inhibitor Nelfinavir Inhibits Kaposi's Sarcoma-Associated Herpesvirus Replication In Vitro

Department of Pediatrics, University of Washington, Seattle, Washington, USA.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 03/2011; 55(6):2696-703. DOI: 10.1128/AAC.01295-10
Source: PubMed


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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