title: The HIV protease inhibitor nelfinavir inhibits Kaposi's sarcoma-associated herpesvirus replication in vitro.
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.
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA.
authors.forename: Soren
authors.initials: S
authors.lastname: Gantt
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Carlsson
authors.forename: Minako
authors.initials: M
authors.lastname: Ikoma
authors.forename: Eliora
authors.initials: E
authors.lastname: Gachelet
authors.forename: Matthew
authors.initials: M
authors.lastname: Gray
authors.forename: Adam P
authors.initials: AP
authors.lastname: Geballe
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Corey
authors.initials: C
authors.lastname: Casper
authors.forename: Michael
authors.initials: M
authors.lastname: Lagunoff
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Vieira
mesh_terms: D000256:Adenoviridae / Q000187:drug effects / Q000502:physiology; D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000187:drug effects / Q000502:physiology; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000187:drug effects*; D006801:Humans; D019888:Nelfinavir / Q000494:pharmacology*; D014616:Vaccinia virus / Q000187:drug effects / Q000502:physiology; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D017320:HIV Protease Inhibitors; D000469:Alkaline Phosphatase; D019888:Nelfinavir