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Journal of Virology, January 2001, p. 1048-1053, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.1048-1053.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

Shoukat H. Qari,1 Saema Magre,2 J. Gerardo García-Lerma,1 Althaf I. Hussain,1 Yasuhiro Takeuchi,2 Clive Patience,2 Robin A. Weiss,2 and Walid Heneine1,*

HIV and Retrovirology Branch, Division of AIDS, STD, and TB Laboratory Research, Centers for Disease Control and Prevention, Atlanta, Georgia,1 and Wohl Virion Centre, Windeyer Institute, University College London, London, United Kingdom2

Received 28 August 2000/Accepted 25 October 2000

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.

* Corresponding author. Mailing address: HIV and Retrovirology Branch, CDC, MS G-19, 1600 Clifton Rd., Atlanta, GA 30333. Phone: (404) 639-0218. Fax: (404) 639-1174. E-mail: WMH2{at}CDC.GOV.

Journal of Virology, January 2001, p. 1048-1053, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.1048-1053.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Shi, M., Wang, X., De Clercq, E., Takao, S., Baba, M. (2007). Selective Inhibition of Porcine Endogenous Retrovirus Replication in Human Cells by Acyclic Nucleoside Phosphonates. Antimicrob. Agents Chemother. 51: 2600-2604 [Abstract] [Full Text]  
  • Miyagawa, S., Nakatsu, S., Nakagawa, T., Kondo, A., Matsunami, K., Hazama, K., Yamada, J., Tomonaga, K., Miyazawa, T., Shirakura, R. (2005). Prevention of PERV Infections in Pig to Human Xenotransplantation by the RNA Interference Silences Gene. J Biochem 137: 503-508 [Abstract] [Full Text]  
  • Toro, C., Rodes, B., Mendoza, C. d., Soriano, V., Macchi, B., Balestrieri, E., Mastino, A. (2003). Lamivudine Resistance in Human T-Cell Leukemia Virus Type 1 May Be Due to a Polymorphism at Codon 118 (V->I) of the Reverse Transcriptase. Antimicrob. Agents Chemother. 47: 1774-1775 [Full Text]  
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