A type C RNA virus was isolated from mink lung cell line (American Type Culture Collection No. CCL 64) which had been cocultivated with 5-bromodeoxyuridine (BUDR)-treated mouse spleen cells. The virus has type C RNA virus morphology as demonstrated by electron microscopy. The complement fixation and immunofluorescent tests performed with mouse anti-p30 antisera show a distinctive difference between mink and mouse type C viruses. Complement fixation tests also indicate that mink type C virus is antigenically different from rat, feline leukemia, feline endogenous (RD-114), baboon, and woolly monkey type C viruses. The virus propagates in cells of mouse, rat, cat, sheep, dog, and human origin, but not in bovine (MDBK) or simian (BSC-1) cells. The infection of rabbit (SIRC) cells and cells of virus origin (mink lung) was followed by delayed and low-titer polymerase release in tissue culture media. The virus sediments in sucrose density gradients as a broad band of densities, 1.13–1.17 g/ml, and contains 70 and 4S RNA. The protein profile is similar to that observed in other mammalian type C viruses. The DNA complementary to the poly(A)-containing virion RNA hybridized to a high degree (72%) with the RNA from virus-producing mink lung cells but not with the RNA from mouse cell lines or uninfected mink lung cell line. The nucleotide sequences homologous to mink viral cDNA were found in mink cell DNA from both virus-producing and nonproducing cells, but not in the DNA of mouse, rat, or feline origin. The virus here described therefore represents an endogenous mink type C virus.

Two newly established human bladder carcinoma cell lines, designated HT-1197 and HT-1376, were characterized. Cells of both cultures exhibited fine structural microvilli and tonofibrils indicative of their epithelial origin. In addition, desmosomes were also present in HT-1197. Marker chromosomes present in HT-1197 and HT-1376 distinguished these from each other and from other known human tumor cell lines. Both cultures grew in soft agar, induced fibrinolytic activity, and were tumorigenic in mice and hamsters. No type C or other virus expression was detected in these cell lines nor in other human urothelial tumors tested.

An Epstein-Barr virus like herpesvirus has been isolated from a lymphoid cell line derived from an orangutan with spontaneous myelomonocytic leukemia. Herpesvirus has not previously been isolated from this species of higher ape.

We investigated the reliability of the fixed cell indirect fluorescent antibody (IFA) peripheral blood smear test as an index of systemic infection with FeLV. Positive results with this test were found to correlate well with detectable FeLV p30 antigen in bone-marrow smears by IFA, in serum and tissue by competition immunoassays, and with type-C particles in bone marrow or spleen by electron microscopy. Most cats with lymphoma, anemia or infectious peritonitis were positive for FeLV and showed a poor or absent antibody response to FeLV p30, gp70, and FOCMA antigens. Most older cats with lymphoma, carcinoma, or sarcoma were negative for FeLV expression and also lacked these FeLV-related antibodies. Detectable immunologic response to FeLV p30 and gp70 proteins and a high-titered FOCMA antibody response were generally restricted to certain healthy cats exposed to FeLV. Antibody to endogenous RD-114 viral p30 and gp70 was not detected in any of a large number of feline sera tested. The prevalence of FeLV-related diseases and immunologic responses to FeLV in healthy cats was directly correlated with the degree of FeLV exposure. By using the IFA blood smear and FOCMA antibody tests one can monitor the horizontal spread of FeLV in multi-cat household and accurately predict the FeLV disease susceptibilty or resistance of individual cats in each environments.

Type C viruses were isolated from embryo cultures of two different rat strains, Sprague-Dawley and Fischer. Both viruses (termed rat leukemia virus, RaLV) were released spontaneously from rat embryo cells, have a density of 1.14 to 1.15 g/cm(3) based on equilibrium sedimentation in sucrose gradients, contain 60-70S RNA, RNA-directed DNA polymerase, and rat type C virus-specific 30,000 molecular-weight-protein determinants. Molecular hybridization studies using the Sprague-Dawley RaLV 60-70S RNA show that the virus-specific nucleotide sequences are present in the DNA of rat embryos. Both Sprague-Dawley and Fischer RaLV can rescue the murine sarcoma virus genome from Kirsten murine sarcoma virus-transformed nonproducer cells and are neutralized by antisera to the RPL strain of RaLV. In contrast to previous RaLV's, these viruses propagate in their own cells of origin as well as in cells of heterologous rat strains.

In several different populations of wild mice, observed over a 35-month period in laboratory geriatric colonies, a direct correlation was found between the prevalence and titer of spleen complement-fixing gs (p30) antigen and C-type particles in newly trapped healthy mice and a predilection to lymphoma and a hind leg paralytic disease upon aging. Other studies have established the indigenous C-type virus as the essential etiological determinant of both diseases in wild mice. An increased incidence of breast carcinomas, hepatomas, and pulmonary adenomas associated with C-type virus also occurred in the lymphoma-paralysis-prone colony as compared with the tumor-resistant colonies.

In certain genetically susceptible populations of wild mice a progressive motor neuron disease with a long latent period is caused by indigenous type C leukemia virus. Neuronal damage appears to be due primarily to a direct neurotropic effect of the virus and not to an immunogenic mechanism. The disease can be prevented by antiviral genetic means. Search for a similar virus in humans with ALS has been negative.

The temperature-sensitive defect in replication of LA334, a double mutant of Rous sarcoma virus, has been characterized both biologically and biochemically. This mutant is complemented for replication at the nonpermissive temperature by both leukosis virus and by RSV(−). Both experiments indicate that LA334 synthesizes functional glycoproteins at the restrictive temperature. This conclusion was confirmed by interference experiments which showed that LA334 induced specific cellular resistance at 41° against superinfection with viruses of subgroup C. Noninfectious virus particles are synthesized at 41° and possess a higher density in sucrose gradients (1.175 g/ml) when compared to those produced at 35° (1.15 g/ml). In addition to the major viral structural proteins these noninfectious virions contain four novel polypeptides, at least three of which appear to be viral in origin. An analysis of viral polypeptide processing indicates that the rate of cleavage of the polyprotein precursor to nonglycosylated structural polypeptides is reduced significantly at the restrictive temperature. Addition of cycloheximide to infected cultures does not prevent the rapid production of infectious virus, seen on shifting cells from the restrictive to the permissive temerature, which suggests that proteins synthesized at 41° can be processed correctly at 35°. Large budding structures that lack the characteristic morphology of C-type particles are visible in electron micrographs of cells infected with the mutant at the nonpermissive temperature. Large virions corresponding in size to some of the budding structures are detectable in negatively stained preparations of noninfectious virus.

Four cell lines were derived from childhood malignancies: rhabdomyosarcoma, sarcoma, lymphosarcoma and an American Burkitt's lymphoma. Cells of the four lines formed tumors in immunosuppressed newborn hamsters. The tumors had a microscopic appearance like that of the tumors from which the cell lines were derived. No virus-like particles were detected by electron microscopy in the cell lines after treatment with bromodeoxyuridine; no hamster type-C virus expression was present in cell lines derived from the hamster tumors. Chromosome constitution and in vitro growth properties of the cell lines were studied as was the fibrinolytic function of the sarcoma lines.

Type-B mammary tumor virus particles were detected by electron microscopy in the submaxillary glands of 6 of 27 freshly trapped, pregnant wild mice (Mus musculus). Type-B particles were also detected in 3 9f 24 seminal vesicles and 2 pulmonary adenomas from wild mice. Intracytoplasmic type-A virus particles were found in 7 spontaneous nonmammary tumors (lymphoma, hepatoma, lung adenoma) of aging wild mice. Type-C virus particles were also detected in many of these tissues.

Wild mice immunosuppressed with antithymocytic sera show a high incidence of disseminated virulent cytomegalovirus infection.

The group‐specific (gs) antigen of RD‐114, an endogenous type‐C virus of domestic cats, was detected by complement fixation (CF) in two of 100 fetal cats and was not detected in any tumors or spleens of postnatal cats. RD‐114 virus was isolated in vitro in RD human sarcoma cells from two of 31 normal cat fetuses but not from any postnatal cat tumors or spleens, with one exception. Feline leukemia virus (FeLV) gs antigen was detected by CF and type‐C particles were seen by electron microscopy (EM) in high prevalence in young cats with lymphoma (65%), anemia (75%) and infectious peritonitis (25%). FeLV gs antigen, type‐C particles and infectious FeLV were occasionally (10‐20%) found in cat fetuses. The general absence of FeLV gs antigen in the endometrium of pregnant cats and the low prevalence of detectable FeLV gs antigen in cat fetuses suggest that the epigenetic transplacental spread of infectious FeLV is not a common occurrence in domestic cats. However, the isolation of FeLV from two pairs of fetal littermates and from the endometria and spleens of both mother cats indicates that such an epigenetic transmission of FeLV can occasionally occur. There was an excellent correlation between detection of RD‐114 and FeLV gs antigen by CF tests in fetal and postnatal tissues and the subsequent isolation in vitro of the corresponding virus. In lymphoma‐ and carcinoma‐bearing cats over 10 years of age, FeLV gs antigen, type‐C particles and infectious virus were seldom found. RD‐114 and FeLV gs antigens or infectious virus were never detected in the same tissues, the same cat or the same litter. These findings are discussed in relation to the natural history of these two different feline type‐C virus genomes.

ONCORNAVIRUS-like morphological structures and particulate material containing RNA-directed DNA polymerase (RDP) activity in association with 70S RNA (commonly referred to as the simultaneous detection1) have been reported in some human milks2–7. However, other workers concluded from electron microscopic studies of human milk that the particles observed were probably cytoplasmic debris and not type-B or type-C virus particles8,9. In addition, the partially purified RDP activity of human milk differed in chromatographic behaviour from that of known animal oncornaviruses10. Thus, the viral origin of the RDP activity measured in human milk remains in doubt. We report here the occurrence of particulate RDP in association with high molecular weight RNA in a small number of human milk samples with no correlation with presence of oncornavirus particles by electron microscopy or with a family history of breast cancer. By contrast, we were able to correlate the presence of high molecular weight RNA and RDP activity with morphologically detectable type-B and type-C oncornaviruses from the milk of freshly trapped wild mice.

Type B virus particles were found by electron microscopy in prelactating breast tissue and milk samples from many recently trapped pregnant wild mice from 3 trapping areas in southern California. Type C virus particles and the corresponding complement-fixing group-specific (gs) antigen were found in low incidence in prelactating breast and spleen tissues of mice from 2 of these areas. However, wild mice from the third trapping area showed a high prevalence of type C particles and gs antigen in these tissues and type C particles in milk. An increased incidence of spontaneous breast tumors, as well as lymphomas, was observed in nonpregnant female wild mice from this third trapping area.

Abstract A high incidence of spontaneous lower-limb paralysis occurred in a population of wild mice (Mus musculus) which had a high incidence of naturally occurring lymphoma and elevated indigenous type-C virus activity. Experimental transmission evidence indicated that both the neurologic and lymphomatous disorders almost certainly were caused by the indigenous type-C virus. The virus appeared to have a direct neurotropic effect on anterior horn neurons in the lower spinal cord.

A neurogenic paralysis of the lower limb can be induced and serially transmitted in mice by a nontransforming type C virus strain that originated in an embryo of a wild mouse. The virus exerted a neurotropic effect on the anterior horn neurons.