Here we report the identification of inbred miniature swine that failed to produce human-tropic replicationcompetent porcine endogenous retroviruses (HTRC PERVs), using in vitro coculture assays. When HTRC PERVs were isolated from transmitting animals, all were recombinant viruses, with the receptor-binding domain of PERV-A combining with PERV-C-related sequences.

Xenotransplantation of porcine tissues has the potential to treat a wide variety of major health problems including organ failure and diabetes. Balanced against the potential benefits of xenotransplantation, however, is the risk of human infection with a porcine microorganism. In particular, the transmission of porcine endogenous retrovirus (

The replication of porcine endogenous retrovirus subgroup A (PERV-A

Natural uranium exposure derives from the mining, milling, and processing of uranium ore, as well as from ingestion of groundwater that is naturally contaminated with uranium. Ingestion and inhalation are the primary routes of entry into the body. Absorption of uranium from the lungs or digestive track is typically low but can vary depending on compound specific solubility. From the blood, two-thirds of the uranium is excreted in urine over the first 24 hours and up to 80% to 90% of uranium deposited in the bone leaves the body within 1.5 years. The primary health outcomes of concern documented with respect to uranium are renal, developmental, reproductive, diminished bone growth, and DNA damage. The reported health effects derive from experimental animal studies and human epidemiology. The Lowest Observed Adverse Effect Level (LOAEL) derived from animal studies is 50 microg/m3 for inhalation and 60 ug/kg body weight/day for ingestion. The current respiratory standard of the Occupational Safety and Health Administration (OSHA), 50 microg/m3, affords no margin of safety. Considering the safety factors for species and individual variation, the ingestion LOAEL corresponds to the daily consumption set by the World Health Organization Drinking Water Standard at 2 microg/L. Based on economic considerations, the United States Environmental Protection Agency maximum contaminant level is 30 microg/L. Further research is needed, with particular attention on the impact of uranium on indigenous populations, on routes of exposure in communities near uranium sites, on the combined exposures present at many uranium sites, on human developmental defects, and on health effects at or below established exposure standards.

PCR amplification of genomic DNA from miniature swine peripheral blood lymphocytes, using primers corresponding to highly conserved regions of the polymerase (pol) gene, allowed the identification of two novel porcine endogenous retrovirus (PERV) sequences, PMSN-1 and PMSN-4. Phylogenetic analyses of the nucleotide sequences of PMSN-1 and PMSN-4 revealed them to be most closely related to betaretroviruses. The identification of PERVs belonging to the Betaretrovirus genus shows that endogenous retroviruses of this family are more broadly represented in mammalian species than previously appreciated. Both sequences contained inactivating mutations, implying that these particular loci are defective. However, Southern blot analysis showed additional copies of closely related proviruses in the miniature swine genome. Analyses of fetal and adult miniature swine tissues revealed a broad mRNA expression pattern of both PMSN-1 and PMSN-4. The most abundant expression was detected in whole bone marrow c-kitprogenitor bone marrow cells, fetal liver, salivary gland, and thymus. It appears unlikely that functional loci encoding these novel PERV sequences exist, but this remains to be established. The betaretrovirus sequences described in this report will allow such investigations to be actively pursued.

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