Xenotransplantation may bridge the widening gap between the shortage of donor organs and the increasing number of patients waiting for transplantation. However, a major safety issue is the potential cross-species transmission of porcine endogenous retroviruses (PERV). This problem could be resolved if it is possible to produce pigs that do not contain replication-competent copies of this virus. In order to determine the feasibility of this, we have determined the number of potentially replication-competent full-length PERV proviruses and obtained data on their integration sites within the porcine genome. We have screened genomic DNA libraries from a Large White pig for potentially intact proviruses. We identified six unique PERV B proviruses that were apparently intact in all three genes, while the majority of isolated proviruses were defective in one or more genes. No intact PERV A proviruses were found in this pig, despite the identification of multiple defective A proviruses. Genotyping of 30 unrelated pigs for these unique proviruses showed a heterogeneous distribution. Two proviruses were uncommon, present in 7 of 30 and 3 of 30 pigs, while three were each present in 24 of 30 pigs, and one was present in 30 of 30 animals examined. Our data indicate that few PERV proviruses in Large White pigs are capable of productive infection and suggest that many could be removed by selective breeding. Further studies are required to determine if all potentially functional proviruses could be removed by breeding or whether gene knockout techniques will be required to remove the residuum.

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Two-day-old chickens of the Arkansas B1 progressor (Pr) line and the B1 regressor (R) line were inoculated intracerebrally with three dilutions of Rous sarcoma virus. Chickens that died between 7 and 42 days postinoculation were examined for lesions attributable to Rous sarcomas. Mortality was 93% for the progressor chickens as compared with 65% for the regressor chicken. Macroscopic lesions were found on the head in 64 chickens, as hemorrhage in the brain in 38, on the heart in 15, on the liver in 9, and in the parenchyma of the brain in one chicken, from a total of 117 chickens inoculated. Surviving chickens were inoculated in the wingweb with Rous sarcoma virus. Of the progressor line chickens three of four developed tumors and two died. The third chicken exhibited abnormal neurological behavior. Of the regressor line, 15 of 20 were immune and of the five that developed tumors, four had complete regressions. The fifth chicken also showed neurological abnormality. The two chickens with neurological dysfunction were sacrificed, and their histopathology examinations revealed lesions in the brain with features belonging to Rous sarcomas, paralleling those reported for other types of sarcomas.