Department of Microbiology, Harvard University School of Public Health, 665 Huntington Avenue. Boston, Massachusetts 02115. USA
Memorial Sloan-Kettering Cancer Center. New York, New York 10025. USA

* Research done in the laboratories of the authors was supported by U.S. National Cancer Institute grants CA-13885. CA-18216, CA-16599, CA-18488. and CA-08748. contract CB-64001 from the U.S. National Cancer Institute. grant DT -32 from the American Cancer Society, and a grant from the Cancer Research Institute. C.K.G. and W.D.H. Jr. are Scholars of the Leukemia Society of America.

A. Introduction

The domestic cat is one of few species where most cases of naturally occurring leukemia and lymphoma are known to be caused by viruses [14]. The RNA retroviruses that cause these diseases are well characterized, and they are related to the viruses that cause similar tumors in laboratory mice [ 13, 15]. The malignancies associated with feline leukemia virus (FeLV) infection include T and B cell lymphomas, lymphoblastic leukemias, and myeloid leukemias [7,44,48,56,63]. Feline sarcoma viruses (FeSV), which are defective for replication. induce multicentric fibrosarcomas and melanomas in vivo [36.62.82], and transform fibroblasts in vitro [5,73]. Many studies on the biology and natural history of feline leukemia have been directed to issues that seem appropriate for a further understanding of leukemia of man. Among these, we have addressed the following questions: a) is leukemia transmitted in a horizontal (infectious) manner or in a vertical (genetic) manner? b) does a specific immunosurveillance response to the tumor cells serve to protect infected cats from leukemia development? c) do tumor cells have tumor specific antigen markers that are expressed in the absence of virus structural proteins? and finally, d) is it possible to establish whether the feline leukemia virus (FeLV) causes lymphoid tumors that neither make virus particles nor express virus structural proteins, nor contain full copies of the viral genome. The latter question appears important to our understanding of any possible role that retroviruses may play in human malignancies since they have generally not been found to be associated with these tumors in man. Recent information gathered in the feline model which relates to these questions will be discussed below.

Summary

In cats, horizontally transmitted viruses cause leukemia and lymphoma under natural conditions. As with other retroviruses, feline leukemia virus (FeLV) contains products of 3 major genes; the virus core gag gene products, the polymerase, and the virus envelope glycoprotein. When cells are transformed in vitro by the related feline sarcoma virus (FeSV), an additional protein, FOCMA is expressed at the cell membrane. FOCMA, which is FeSV-coded, is transformation and/ or tumor specific and expressed regardless ofwhether or not the cells make virus or contain virus structural antigens. Lymphoid leukemia cells also express FOCMA, both when FeLVis used to induce the disease in laboratory cats and when the tumors occur under natural conditions. FOCMA is expressed on both T and B lymphoid leukemia cells, but not expressed on non-malignant lymphoid cells, even when they are infected with FeLV. About one-third of the naturally occurring lymphoid tumors of cats lack detectable FeLV proteins and varying portions of the FeLV provirus. Despite this, they regularly express FOCMA, which is the target of an immunosurveillance response that functions effectively under most conditions. FOCMA thus provides a useful model for antigens that might be expressed in "virus-negative" leukemias of man.