Replication of Mouse-Tropic and Xenotropic Strains of Murine Leukemia Virus in Human × Mouse Hybrid Cells

The replication of mouse-tropic and xenotropic strains of murine leukemia virus in human x mouse hybrid cells was investigated. NB-tropic strains of the leukemia virus replicated efficiently in several hybrid lines, including those that contained a complete complement of human chromosomes and many mouse chromosomes. In lines with only a few mouse chromosomes, NB-tropic viruses failed to replicate. N- and B-tropic viruses replicated in human x N-type and human x B-type cells, respectively. The N- and B-tropic viruses replicating in these hybrid cells retained their original tropism. The viral restrictive functions of the mouse Fv-1 locus were expressed in the hybrid cells, restricting the replication of N- and B-tropic strains in human x B-type and human x N-type mouse cells, respectively. In contrast to mouse-tropic viruses, AT-124 virus, a xenotropic strain, replicated in human but not in mouse cells or in hybrid cells containing a complete complement of human chromosomes and near complete complement of mouse chromosomes However, hybrid lines with only a few mouse chromosomes supported AT-124 replication. Thus, human genes in hybrid cells do not restrict the replication of mouse or xenotropic murine leukemia virus strains, while mouse genes in such cells restrict xenotropic leukemia virus replication and, as determined by the mouse Fv-1 phenotype, mouse-tropic murine leukemia virus. These results indicate that exogenously applied mouse-tropic and xenotropic oncornaviruses exhibit different patterns of restriction in human-mouse hybrid cells and that such hybrid cells may be used for genetic analysis of oncornavirus replication.