Seroepidemiology of human T-lymphotropic virus type III among homosexual men with the acquired immunodeficiency syndrome or generalized lymphadenopathy and among asymptomatic controls in Boston.

We studied a cohort of 45 homosexual men with the acquired immunodeficiency syndrome, 78 with persistent unexplained generalized lymphadenopathy, and 160 asymptomatic homosexual controls for serologic evidence of infection with human T-lymphotropic virus type III (HTLV-III). Study participants were recruited from a community-based health center and a university hospital practice. Ninety-eight percent of men with the syndrome and greater than 90% of men with generalized lymphadenopathy had antibody to HTLV-III, while 21% of the controls were positive (p less than 0.001). Six patients with generalized lymphadenopathy developed the acquired immunodeficiency syndrome over 2 years; all were seropositive for HTLV-III. Thirty-six asymptomatic controls had had sexual contact with a man with the syndrome; receptive anal intercourse in this group was associated with seropositivity for HTLV-III. These data suggest that persistent generalized lymphadenopathy and the acquired immunodeficiency syndrome are part of a clinical spectrum of HTLV-III infection and that most high-risk homosexual men in some regions of the United States have not yet been infected with this virus.

Human melanoma cells have both nerve growth factor and nerve growth factor-specific receptors on their cell surfaces.

Human melanoma cells were examined in an indirect membrane immunofluorescence assay for surface nerve growth factor (NGF) and NGF receptors. This assay revealed that human melanoma cells have various levels of NGF and NGF receptors on the plasma membrane, whereas a variety of human sarcoma and carcinoma tumor cells and normal human fibroblasts are negative. Surface NGF could be detected on melanoma cells with a rabbit antiserum directed to NGF at titers as high as 1:64; prior adsorption of this antibody with mouse 2.5S NGF resulted in a loss of fluorescence. The melanoma cells were positive whether or not they were grown in the presence of fetal calf serum. NGF production by human melanomas is a previously unrecognized property of this differentiated cell type. Although other cells in culture have been shown to produce NGF, the association of NGF production with the presence of NGF receptors on the cell surface is rare among tumor cells, and may represent an opportunity for "autostimulation" of melanoma cells by this growth factor.

Leukemia specific antigens: FOCMA and immune surveillance.

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 of whether or not the cells make virus or contain virus structural antigens. Lymphoid leukemia cells also express FOCMA, both when FeLV is 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 immuno-surveillance 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.

Feline oncornavirus-associated cell membrane antigen: evidence for an immunologically crossreactive feline sarcoma virus-coded protein.

The feline oncornavirus-associated cell membrane antigen (FOCMA) acts as a target for natural immuno-surveillance against tumor development in the cat. In the present study, mink and rat cells nonproductively transformed by feline sarcoma virus (FeSV) were shown to express FOCMA as well as 5'-terminal feline leukemia virus (FeLV) gag gene proteins, p15 and p12. In contrast, such cells lack detectable levels of other FeLV gag gene-coded proteins or the env gene product, gp70. FOCMA, p15, and p12 antigen expression is initially in the form of an 80,000-100,000 molecular weight precursor which, upon post-translational cleavage, gives rise to a 65,000 molecular weight component that contains FOCMA and a 25,000 molecular weight component containing p15 and p12. Feline lymphoma cells, including those from several tumors that lacked detectable levels of FeLV structural protein expression, were shown to be FOCMA-positive. These findings strongly suggest that FOCMA represents an FeSV-coded transformation specific protein and provide preliminary information regarding the position within the FeSV genome coding for its synthesis.

Feline oncornavirus-associated cell membrane antigen: expression in transformed nonproducer mink cells.

The feline oncornavirus-associated cell membrane antigen (FOCMA) is a target for naturally occurring immunity that protects the cat against development of fibrosarcoma and leukemia. Feline sarcoma virus-transformed "nonproducer" mink cells express high levels of FOCMA, but not the major viral structural proteins. Transformation of the same cells by murine sarcoma virus, or infection with feline leukemia virus, which is nontransforming for epithelial or fibroblastic cells, did not induce FOCMA. Thus, FOCMA expression in mind lung cells is specifically associated with transformation by feline sarcoma virus.

Horizontal transmission of feline leukemia virus under natural conditions in a feline leukemia cluster household.

Ten post-weanling 4-month-old cats, designated "tracers", were placed in a feline leukemia cluster household to determine the efficiency of horizontal transmission of feline leukemia virus (FeLV). The tracer cats were confirmed as negative for prior exposure to FeLV. Following the placement in the leukemia cluster environment, the tracer cats were serologically monitored at intervals of 3-6 weeks for a total period of 1 year. The tests employed included the detection of FeLV using fixed-cell immunofluorescence and the detection and titration of antibody to : (1) the feline oncornavirus-associated cell membrane antigen (FOCMA), as detected by membrane immunofluorescence; (2) viable FeLV, using serum neutralization; (3) virion core protein p30, using radioimmunoprecipitation; and (4) virion glycoprotein gp70, using radioimmunoprecipitation. All of the tracers had evidence of horizontal infection by FeLV, by several criteria. Seven of the 10 had virus that could be isolated from plasma. All of these 7 developed a terminal illness within 18 months; 3 developed aplastic anemia, 3 infectious peritonitis, and 1 lymphoma. The remaining 3 were negative for FeLV by both virus isolation and fixed-cell immunofluorescence. These 3 did, however, develop high antibody titers by all four criteria and they remained healthy throughout the examination period. These results clearly indicate that unprotected pros-weanling cats brought into a leukemia exposure household environment have a high risk of becoming infected with FeLV. Furthermore, a large proportion of the cats are at risk for development of persistent viremia and FeLV-related diseases.