Evelyn E. Zuckerman

Infection with Human T-Cell Leukemia Virus Type I in Patients with Leukemia

Among 211 adults with leukemia who received multiple transfusions, 6 were found to be seropositive for human T-cell leukemia virus Type I (HTLV-I). Before the positive serum specimens were obtained, these patients received a mean of 14 units of red cells and 78 units of platelets. Seroconversion could be documented in three patients. None of the 6 patients seropositive for HTLV-I had a T-cell leukemia, other illnesses attributable to HTLV-I infection, or risk factors for HTLV-I infection other than transfusion: none were seropositive for human immunodeficiency virus. Patients with leukemia who receive multiple transfusions appear to be at risk for HTLV-I infection.

The feline oncornavirus-associated cell membrane antigen (FOCMA) is related to, but distinguishable from, FeLV-C gp70

The feline oncornavirus-associated cell membrane antigen (FOCMA) on the surface of feline lymphosarcoma (LSA) cells is defined as the target(s) recognized in immunofluorescence (IFA) tests by antibody in sera of cats relatively resistant to development of FeLV (feline leukemia virus) LSA and FeSV (feline sarcoma virus) fibrosarcoma. The specificities of antibodies in cat FOCMA-typing sera and the nature of the LSA antigens recognized were investigated in the present study. FOCMA sera obtained from viremic cats were separable into at least two classes : those which contained antibodies against the envelope glycoprotein (gp70) of subgroup C FeLV and those which did not contain antibodies against any subgroup of FeLV. The first class of sera could be further subdivided into three groups: those whose FOCMA reactivity could be completely absorbed, partially absorbed, or not absorbed by FeLV-C antigens. The second class of sera could be further subdivided into two groups: those whose FOCMA reactivity could be partially absorbed and those whose activity could not be absorbed by FeLV-C. The results indicate that the FOCMA reactivity exhibited by some viremic cat sera can be partially, if not entirely, attributed to antibodies not crossreactive with FeLV virion antigens. A consistent property of all FOCMA sera in this study is the ability to bind to 70-kDa proteins on the surface of LSA cells. Staphylococcus aureus V8 protease partial digest maps of 70-kDa proteins purified from 12 primary feline LSAs (five FeLV positive and seven FeLV negative) all showed 18-, 14-, and 10-kDa fragments. V8 maps of FeLV-C gp70 showed similarly sized fragments while the maps of the RD114, FeLV-A, and FeLV-B gp70s were distinct. However, in a subgroup-specific radioimmunoassay for FeLV-C gp70-related antigens, the LSA 70-kDa proteins were found to be serologically related to, but distinct from, FeLV-C gp70. The results on the antigenic variations among LSA 70-kDa proteins and the antibodies which bind them are entirely consistent with previous studies indicating heterogeneity among FOCMA determinants.

The epidemiology of the feline leukemia virus (FeLV).

Clustering of cases of feline lymphosarcoma (LSA) has been observed by veterinarians for many years. In 1964 it was discovered that feline LSA was caused by an oncornavirus, the feline leukemia virus (FeLV). In 1970, a simple, indirect immunoflourescent antibody (IFA) test for FeLV was developed which enabled large numbers of cats, living in their natural (household) environments, to be tested for the virus. In one study, over 2,000 cats were tested and the results showed conclusively that FeLV is a contagious agent for cats. This finding was independently confirmed by several other investigators using different testing procedures. After discovering the contagious nature of FeLV a test and removal program was devised which successfully prevents the spread of FeLV and the development of FeLV diseases in the pet cat population. There is, at present, no evidence that FeLV infects humans living with FeLV infected cats.

Isolation of a new feline sarcoma virus (HZ1-FeSV): Biochemical and immunological characterization of its translation product

A new strain of feline sarcoma virus, designated HZ1-FeSV, was isolated from a 4-year-old domestic cat with multicentric fibrosarcoma. A primary tumor cell line was established and virus produced from that line was found to induce foci in feline embryonic lung fibroblasts (FLF3) and mink lung fibroblasts (CCL64) in tissue culture and fibrosarcomas in inoculated 10-week-old kittens. The derivation of transformed nonproducer clones of FLF3 and CCL64 cells containing helper virus-rescuable, focus-forming activity indicated that HZ1-FeSV was defective for replication. The only discernible translation product of the HZ1-FeSV genome in cultured cells was a 100,000-Da polyprotein (P100) which contained amino-terminal sequences of the FeLV gag gene precursor protein covalently linked to a sarcoma virus-specific domain. Immunoprecipitates containing P100 exhibited a protein kinase activity capable of phosphorylating tyrosine residues of P100. Immunologically, P100 was highly cross-reactive with gag-fes polyproteins encoded by two previously characterized strains of FeSV, the GA- and the ST-FeSV. By comparison of methionine-containing tryptic peptides, the HZ1-FeSV protein was shown to be more closely related to the GA-FeSV protein than to the ST-FeSV protein, but to be distinguishable from both other proteins.

Immunological and Biochemical Characterization of HZ2 Feline Sarcoma Virus and Abelson Murine Leukaemia Virus Translation Products

The extent of homology between the translation products of the HZ2 strain of feline sarcoma virus (HZ2-FeSV) and the Abelson murine leukaemia virus (A-MuLV) was examined immunologically and biochemically. Antiserum prepared against the v-abl-encoded determinants of the A-MuLV polyprotein P120gag-abl was also found to precipitate specifically the 98K mol. wt. HZ2-FeSV protein (P98gag-abl). The basis for this immunological crossreactivity was indicated by the findings that the two proteins had at least six [35S]methionine-containing tryptic peptides and at least eight [35S]methionine-containing chymotryptic peptides in common. Each of the two proteins also had tryptic and chymotryptic peptides which were unique. Both proteins were associated with tyrosyl kinase activities which exhibited some similar biochemical properties in vitro. However, the HZ2-FeSV-associated activity was much more sensitive to competitive inhibition by nucleoside and deoxynucleoside diphosphates than was the A-MuLV-associated activity. These results suggest that, while the gag-abl translation products of these two independent isolates of transforming retrovirus are highly related structurally and functionally, the differences in structure contribute to differences in enzyme activity. Further comparative studies of these two proteins should play an important role in determining their roles in induction of two different types of malignancy: lymphosarcoma in the case of the A-MuLV protein and fibrosarcoma in the case of the HZ2-FeSV protein.