Lymphomas associated with a tolerant lymphocytic choriomeningitis virus infection in mice.

On each of 2 occasions when a tolerant lymphocytic choriomeningitis (LCM) virus infection was introduced experimentally by a natural route into breeding stock of the Pirbright P(SD) mouse strain, and a comparison made with genetically identical controls, where was in successive generations an overall 15-fold increase in the incidence of lymphomas. Most of these were recognized clinically after the age of 16 months. The same observation was made in mice of the P(H) strain from which the P(SD) strain had been surgically derived. The finding is interpreted as the activation of an endogenous viral oncogene by the LCM infection. It was concurrently observed that the incidence of mammary tumours in the P(H) strain mice before the age of 16 months was markedly lower in the animals infected with LCM.

The potential of recombination for the production of foot-and-mouth disease virus vaccine strains.

Biological proof of recombination in foot-and-mouth disease virus has been provided by studies on a large suite of conditional lethal mutants and a recombination map of approximately 70 mutations has been produced. However, recombination is a highly variable phenomenon and this has cast doubt on its validity and certainly on its applicability to such practical purposes as the production of good vaccine strains. Evidence is presented to demonstrate (1) that the genetic map has a good correlation with the biochemical map of polypeptide coding sequence for the genome and (2) that recombinants can be isolated bearing biochemical and biological markers from both parents. Finally, the analysis of 36 recombinants from a cross involving a cattle-attenuated and a cattle-virulent virus is described. These results have enabled us to identify the location of biological properties such as a mouse virulence and good growth in BHK cells on the genome of these two parent viruses.

A barrier cabinet for mice based on the Houghton chicken isolator.

Nuclei of a disease-free foundation stock of mice housed in a barrier unit and a barrier cabinet constructed from resin-bonded glass-fibre were compared over a period of 7 years. The cabinet was found to be a satisfactory alternative to a flexible-film isolator and was thought to be preferable. A description is given of the cabinet, the method of sterilization and the breeding schedules for 2 generations adopted to make the maximum use of the 10-month life of the high-efficiency filter employed. Throughout many cycles of this duration the degree of cleanliness was of a high order. A major contribution towards this was the collection of excreta on a tray lined with both absorbent and grease-proof paper, and the removal from the cabinet of dirt boxes when weaners were issued in them at the age of 5 weeks. These boxes were replaced in the cabinet by clean, sterile ones.

Epidermal tissue as a primary site of replication of lymphocytic choriomeningitis virus in small experimental hosts.

When fresh urine from LCM tolerantly infected mice was applied to small areas of excoriated skin of guinea-pigs undiluted or diluted 10(-1), a high LCM infectivity developed in the local dermal tissue within 3 days and quickly spread to the lymphatic system. The skin at this site of infection became erythematous 10--12 days after infection and a few days later a rash was often seen in the hairless skin around the mammary teats. A viraemia was first detected at about 8 days after infection and persisted for at least 8 days, during which time a high infectivity titre in skin not only at the infection site but also distal to it suggested that there was a generalized active infection of the dermis. Infectivity in the tongue was simultaneously high and probably associated with erosions of the tongue tip seen a day or two later than the teat rash. In similar experiments in hamsters and rabbits, indications were again that lightly injured dermis was a primary site of virus replication. These observations should lead to the dermal route receiving greater attention as a potential route of infection of man when exposed to infectious excretions of reservoir hosts of arena-viruses.

Murine lymphocytic choriomeningitis: the history of a natural cross-infection from wild to laboratory mice.

A new locus of wild house mice tolerantly infected with the virus of lymphocytic choriomeningitis (LCM) has been identified in the United Kingdom. Evidence is presented which indicates that these mice were the source of infection in a laboratory mouse breeding colony, the mode of transmission probably being bites on tails and limbs exposed through wire-grid flooring. The results of an experiment which simulated indirect exposure of SPF mice to tolerantly infected wild mice supported earlier observations that without injury to the epidermis the risk of spread of infection from the infective urine, saliva or faeces is low.

The hamster as a secondary reservoir host of lymphocytic choriomeningitis virus.

Exposure of weaned hamsters to an environment contaminated with LCM virus shed by tolerantly infected mice led to short subclinical infections. If infection occurred in early pregnancy, the young appeared normal at birth but their tissues were highly infective. For two to three months their bites and urine were also highly infective. A viraemia did not persist long enough for successive vertical transmissions of the infection to be likely. However, the viruria persisted in most prenatally infected hamsters for at least eight months and under simulated field conditions was a potent virus source for contact infections, leading to further generations of prenatally infected young. In the absence of the natural reservoir host, such long-term carriers could have been a major factor in causing the build-up of infection in colonies of hamsters which, when purchased as household pets, led to a recent spate of human clinical infections in Germany and the U.S.A.