Denner J, Specke V, Tacke S, Özel M (2002): Porcine endogenous retroviruses (PERVs): Diagnostic assays, adaptation to human cells and infection experiments with small animals and non-human primates
Transplant. Med. 14 (3): 171-183.

PERVs are present as numerous copies in the genome of all pig strains. At least three of them, PERV-A, PERV-B, and PERV-C are produced as virus particles and two, PERV-A and PERV-B, infect human cells in vitro. To address the potential for adaptation of PERV as it spreads from pig cells to human cells in a xenotransplant recipient, different PERVs were serially passaged on human cells, among them a recombinant virus containing a PERV-C LTR and a PERV-A receptor-binding site. An increase in virus titre and genetic changes in the LTR were observed. Similar changes in the LTR of related retroviruses were associated with increased tumourigenicity. Recombinant viruses containing genetically altered LTRs were not found in the pig genome and in order to discriminate them from PERVs released from pig cells they should be designated as human-adapted PERVs (HAPs). To evaluate the potential risk coming from PERVs during xenotransplantation, host range studies were performed in vitro and in vivo. In vitro, cell lines and primary cells of different species (cat, mink, rhesus monkey, baboon, man) could be infected productively. However, in vivo rats immunosuppressed by cyclosporin A and treated with cobra venom factor to deplete the complement system, minks, and guinea pigs were not infected. No antibodies against PERV and no provirus integration were observed in inoculated animals. Of all animal models, non-human primates are of major value due to their close genetic relationship to man. Three non-human primate species (rhesus monkey, baboon, pig-tailed monkey) were inoculated with PERV in vivo and showed no evidence of infection despite the daily immunosuppression using cyclosporine A, RAD (a rapamycine derivative) and steroids and despite the high doses of virus inoculated. Western blot assays did not reveal any presence of antibody reactivity against PERV and no provirus integration was observed by PCR. Using the same methods, no evidence of PERV infection was obtained when first xenotransplantation patients and butchers with close contact to pigs were studied. It should be underlined, that in contrast to the situation five years ago meanwhile highly sensitive and specific methods have been developed which allow monitoring for PERV infections during experimental and clinical xenotranplantations.