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

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 (IC 50 s and IC 90 s, 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 IC 50 s, 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 culturebased, 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 IC 50 s for WT HIV-1. Thus, following screening of many antiretroviral agents, our findings support only the potential clinical use of zidovudine.

Restriction of Porcine Endogenous Retrovirus by Porcine APOBEC3 Cytidine Deaminases

“…These include the use of nontransmitter pigs or pigs without active PERV loci as source animals, use of antiretroviral agents, such as the reverse transcriptase (RT) inhibitors zidovudine (AZT) and dideoxyinosine (ddI) in recipients (80,81), viral vaccines, and antibodies to target PERV (22), or the reduction of viral replication in vitro using RNA interference (16).…”

Promoter activity analysis and methylation characterization of LTR elements of PERVs in NIH miniature pig

“…Furthermore, approaching of chemotherapy is also very important. Inhibitors of HIV reverse transcriptase could be used against the PERV reverse transcriptase (Powell et al, 2000;Qari et al, 2001). However, protease inhibitors of HIV do not exert inhibitory effects on PERV protease (Blusch et al, 2002).…”

Del alotransplante al xenotransplante: la compatibilidad antigénica donante-receptor por medio del Complejo Mayor de Histocompatibilidad CMH

“…Estas moléculas tienen a cargo la presentación de antígenos exógenos (bacterias, hongos, parásitos, etc) a los linfocitos T CD4+ o LT ayudador implicado en la respuesta inmune. Los genes que codifican las síntesis de moléculas Clase II son HLA D, DR, DO, DP, DQ, DM, DN, DZ (6,9,(18)(19).…”