Molecular cloning of integrated caprine arthritis-encephalitis virus

A full-length DNA clone of the exogenous retrovirus, caprine arthritis-encephalitis virus (CAEV), was isolated from high molecular weight DNA of CAEV-infected Himalayan tahr ovary cells. Although other restriction maps of CAEV have been published, this is the first time that the proviral DNA has been cloned. The restriction enzyme map of the clone was determined and found to be identical to that of unintegrated linear CAEV DNA except for the presence of cellular flanking sequences. These findings establish that lentiviruses are able to integrate within the infected host cellular genome. The cloned CAEV genome was shown to contain terminal repeats of approximately 450 base pairs in length, and its restriction enzyme map was oriented with respect to the direction of viral RNA transcription. When the cloned CAEV DNA was used as a molecular probe, it failed to detect related proviral sequences in the genomes of a variety of vertebrate species, including the goat, sheep, horse, mouse, and man. When CAEV DNA was hybridized under relaxed conditions to a variety of cloned DNAs, representing different oncoviral genera, homology to mouse mammary tumor virus (MMTV) was observed, while no homology to avian type C or mammalian type A, C, and D retroviruses was detected. This homology was localized to a region in MMTV corresponding to the 3′ end of the gag gene and the 5′ end of the pol gene.