Selective inhibition of porcine endogenous retrovirus replication in human cells by acyclic nucleoside phosphonates

Abstract

Several anti-human immunodeficiency virus type 1 reverse transcriptase inhibitors were evaluated for their antiviral activities against porcine endogenous retrovirus in human cells. Among the test compounds, zidovudine was found to be the most active. The order of potency was zidovudine > phosphonylmethoxyethoxydiaminopyrimidine = phosphonylmethoxypropyldiaminopurine > tenofovir > or = adefovir > stavudine.

FIG. 1.

Inhibitory effects of selected compounds on PERV replication in 293T cells. 293T cells were infected with PERV derived from PK15 cells and cultured in the presence of various concentrations of (A) AZT, (B) PMEO-DAPy, (C) d4T, (D) PMPDAP, (E) 3TC, and (F) NVP. After a 24-h incubation, the cells were collected and genomic DNA was extracted. Quantitative real-time PCR was performed to determine the amount of PERV proviral DNA in the infected cells using a primer pair and probe specific to the PERV pol gene (lines). The viable-cell number was determined by a tetrazolium dye cell proliferation assay (bars). The PCR and cell proliferation assays were performed in triplicate and in duplicate, respectively. The data represent means plus standard deviations. Representative results for two or three independent experiments are shown.

FIG. 2.

Amino acid sequences of the polymerase domain of PERV RT derived from PK15 and KK5 cells. The catalytic site is indicated by boldface letters.