Robert W. Rongey

A Spontaneous Lower Motor Neuron Disease Apparently Caused by Indigenous Type-C RNA Virus in Wild Mice

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.

Isolation of a Neurotropic Type C Virus

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.

An avian sarcoma virus mutant that is temperature sensitive for virion assembly

Abstract 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.

Childhood sarcomas and lymphomas. Characterization of new cell lines and search for type-C virus.

Four cell lines were derived from childhood malignancies: rhabdomyosarcoma, sarcoma, lymphosarcoma and an American Burkitts 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.

Endogenous type C RNA virus of mink (Mustela vison).

Abstract 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.