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Susceptibility of the Porcine Endogenous Retrovirus to Reverse Transcriptase and Protease Inhibitors

By Shoukat H. Qari, Saema Magre, J. Gerardo García-Lerma, Althaf I. Hussain, Yasuhiro Takeuchi, Clive Patience, Robin A. Weiss and Walid Heneine

Abstract

Porcine xenografts may offer a solution to the shortage of human donor allografts. However, all pigs contain the porcine endogenous retrovirus (PERV), raising concerns regarding the transmission of PERV and the possible development of disease in xenotransplant recipients. We evaluated 11 antiretroviral drugs licensed for human immunodeficiency virus type 1 (HIV-1) therapy for their activities against PERV to assess their potential for clinical use. Fifty and 90% inhibitory concentrations (IC50s and IC90s, respectively) of five nucleoside reverse transcriptase inhibitors (RTIs) were determined enzymatically for PERV and for wild-type (WT) and RTI-resistant HIV-1 reference isolates. In a comparison of IC50s, the susceptibilities of 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. Tissue culture-based, single-round infection assays using replication-competent virus confirmed the relative sensitivity of PERV to zidovudine and its resistance 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 IC50s for WT HIV-1. Thus, following screening of many antiretroviral agents, our findings support only the potential clinical use of zidovudine

Topics: Vaccines and Antiviral Agents
Publisher: American Society for Microbiology
Year: 2001
DOI identifier: 10.1128/JVI.75.2.1048-1053.2001
OAI identifier: oai:pubmedcentral.nih.gov:114002
Provided by: PubMed Central
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