Endogenous mouse leukemia viruses.

Abstract

The earlier demonstration that genes of the mouse greatly influenced the spontaneous incidence of lymphoma was among the more persistent barriers to general acceptance of a viral etiology of this disease. We now can be fairly certain that some of those mouse genes are the DNA life phase of a class of retrovirus known as murine leukemia virus. These MuLV, although related in sequence to each other, are a collection of viruses that show diverse patterns of host range and tissue tropisms. The host-range properties of MuLV serve as means of classifying them into related families known as ecotropic, xenotropic, and amphotropic, and are probably dictated by determinants on gp70. The preferential abilities to replicate in different tissues, on the other hand, may be dictated by the controlling sequences located at the 3' end of the genome, known as U3. MuLV genomes are located at many different sites in the mouse genome. The viral genomes found at those sites can be induced to be expressed with different efficiencies spontaneously in vivo, by chemicals in vitro, or by DNA transfection. Certain MuLV genomes can also interact to increase expression perhaps by recombination or trans complementation. Although the molecular mechanisms that explain these phenomena are not yet clear, the phenomenon of differential expression has important pathological consequences, particularly in the development of lymphoma. The complex process by which endogenous MuLV induce leukemia appears to involve the expression and interaction of multiple MuLV genomes. It seems apparent that expression of an MCF-like gp70 is an invariant aspect of this process, and that observation suggests that this molecule, like the SFFV gp52, may indeed serve to stimulate cell proliferation. The most common means of expressing such a molecule at elevated levels appears to involve recombining it into an ecotropic genome that replicates with high efficiency. Thus, the viral requirements for leukemogenesis may depend on both efficient and perhaps tissue tropic replication as well as on the expression of a particular gp70.(ABSTRACT TRUNCATED AT 400 WORDS)