title: Susceptibility of porcine endogenous retrovirus to anti-retroviral inhibitors.
abstract: Porcine endogenous retrovirus (PERV) is an endogenous retrovirus that poses a risk of iatrogenic transmission in the context of pig-to-human xenotransplantation. The lack of a means to control PERV infection in the context of pig-to-human xenotransplantation is a major concern in the field. In this study, we set out to evaluate the ability of currently licensed anti-HIV drugs, and other types of anti-retroviral compounds, to inhibit PERV infection in vitro.
  
  
  
  We used target cells stably expressing one of the known PERV viral receptors, an infectious molecular clone, PERV-A 14/220, and at least one drug from each class of anti-retroviral inhibitors as well as off-label drugs shown to have anti-viral activities. The susceptibility of PERV-A 14/220 LacZ to the anti-retroviral drugs was determined from infected cells by histochemical staining.
  
  
  
  We extend the results of previous studies by showing that, in addition to raltegravir, dolutegravir is found to have a potent inhibitory activity against PERV replication (IC50 8.634 ±0.336 and IC50 3.06 ± 0.844 nM, respectively). The anti-HIV drug zidovudine (AZT) showed considerable anti-PERV activity with IC50 of 1.923 ±0.691 μM as well.
  
  
  
  The study results indicate that some of the licensed anti-retroviral drugs may be useful for controlling PERV infection. However, the efficacy at nanomolar concentrations put forward integrase inhibitors as a drug that has the potential to be useful in the event that xenotransplantation recipients have evidence of PERV transmission and replication.
authors.affiliation: Gene Transfer and Immunogenicity Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, MD, USA.
authors.forename: Takele
authors.initials: T
authors.lastname: Argaw
authors.affiliation: Gene Transfer and Immunogenicity Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, MD, USA.
authors.forename: Winston
authors.initials: W
authors.lastname: Colon-Moran
authors.affiliation: Gene Transfer and Immunogenicity Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, MD, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Wilson
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D002478:Cells, Cultured; D020077:Endogenous Retroviruses / Q000187:drug effects*; D011817:Rabbits; D013552:Swine; D014183:Transplantation, Heterologous / Q000379:methods; D014777:Virus Diseases / Q000188:drug therapy / Q000517:prevention & control*
chemical_list: D044966:Anti-Retroviral Agents
keywords: anti-retroviral; porcine endogenous retrovirus; xenotransplantation