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. 2001 Jan;75(2):1048-53.
doi: 10.1128/JVI.75.2.1048-1053.2001.

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

S H Qari  1 , S Magre, J G García-Lerma, A I Hussain, Y Takeuchi, C Patience, R A Weiss, W Heneine
Affiliations

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

S H Qari et al. J Virol. 2001 Jan.

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

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Figures

FIG. 1
FIG. 1
Susceptibility of HIV-1 and PERV to PIs by a Gag protein-processing inhibition assay. (A) Immunoblot of HIV-1-infected OM-10.1 cells treated with different concentrations of indinavir and nelfinavir (first lane, no treatment). Positions of Gag proteins are indicated. (B) Immunoblot of PERV-293 cells untreated (first lane) and treated with different concentrations of nelfinavir and indinavir.
FIG. 2
FIG. 2
Alignment of portions of HIV-1 and PERV RT amino acid sequences. Identical residues are indicated with an asterisk. Four D residues (codons 110, 113, 185, and 186) and the LPQG motif (codons 149 to 152) conserved among the retroviruses are underlined (34a). The HIV-1 polymerase active-site YMDD (codons 183 to 186) is in bold. Codons associated with resistance of HIV-1 to multinucleoside analogs (Q151M), nevirapine (Y181C), lamivudine (M184V), and zidovudine (T215Y/F) are shaded.
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References

    1. Akiyoshi D E, Denaro M, Zhu H, Greenstein J L, Banerjee P, Fishman J A. Identification of a full-length cDNA for an endogenous retrovirus of miniature swine. J Virol. 1998;72:4503–4507. - PMC - PubMed
    1. Black P L, Downs M B, Lewis M G, Ussery M A, Dreyer G B, Petteway S R, Lambert D M. Antiretroviral activities of protease inhibitors against murine leukemia virus and simian immunodeficiency virus in tissue culture. Antimicrob Agents Chemother. 1993;37:71–77. - PMC - PubMed
    1. Boden D, Markowitz M. Resistance to human immunodeficiency virus type 1 protease inhibitors. Antimicrob Agents Chemother. 1998;42:2775–2783. - PMC - PubMed
    1. Butera S T, Roberts B D, Lam L, Hodge T, Folks T M. Human immunodeficiency virus type 1 RNA expression by four chronically infected cell lines indicates multiple mechanisms of latency. J Virol. 1994;68:2726–2730. - PMC - PubMed
    1. Chari R S, Collins B, Magee J, DiMaio J, Kirk A, Harland R, McCann R, Platt J, Meyers W. Treatment of hepatic failure with ex vivo pig-liver perfusion followed by liver transplantation. N Engl J Med. 1994;331:234–237. - PubMed

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