Susceptibility of the porcine endogenous retrovirus to reverse transcriptase and protease inhibitors

Porcine xenografts mag offer a solution to the shortage of human donor allo grafts. However, all pigs contain the porcine endogenous retrovirus (PERV), raising concerns regarding the. transmission of PERV and the possible deve lopment of disease in xenotransplant recipients. We evaluated II antiretrov iral drugs licensed for human immunodeficiency virus type 1 (HIV-1) therapy for their activities against PERV to assess their potential for clinical u se. Fifty and 90% inhibitory concentrations (IC(50)s and IC(90)s, respectiv ely) of five nucleoside reverse transcriptase inhibitors (RTIs) were determ ined were enzymatically for PERV and for wild-type (WT) and RTI-resistant H IV-1 reference isolates. In a comparison of IC(50)s, the susceptibilities o f PERV RT to lamivudine, stavudine, didanosine, zalcitabine, and zidovudine were reduced >20-fold, 26-fold, 6-fold, 4-fold, and 3-fold, respectively, compared to those of WT HIV-1. PERV was also resistant to nevirapine. Tissu e culture-based, single-round infection assays using replication-competent virus confirmed the relative sensitivity of PERV to zidovudine and its resi stance to all other RTIs. A Gag polyprotein-processing inhibition assay was developed and used to assess the activities of protease inhibitors against PERV. No inhibition of PERV protease was seen with saquinavir, ritonavir, indinavir, nelfinavir, or amprenavir at concentrations >200 fold the IC(50) s for WT HIV-1. Thus, following screening of many antiretroviral agents, ou r findings support only the potential clinical use of zidovudine.