Neurotropic virus growth and nature of effect on host tissue phosphates

The growth rate of several different neurotrophic viruses in mouse brain tissue in vivo have been studies and the association of virus growth and morbidity of the infected animals noted: 1. Lymphocytic Choriomeningitis virus grew at a logarithmic rate for the first 72 hours after inoculation. The virus growth than appeared to "Plateau" and even decrease subsequently. Morbidity and mortality were not evident before 144 hours after infection. 2. St Louis encephalitis virus was also observed to have a logarithmic rate of increase which achieved its maximum of 96 hours or less. The virus growth showed a latent period after inoculation which appeared to decrease in duration with the number of virus passages. The time necessary for maximal titre was reduced accordingly (72 hours). The time at which symptoms became evident (72 to 120 hours) or death occurred (96 to 144 hours) did not seem directly related to the titre of the virus in the tissues, but rather to the time at which measurable growth was first observed. 3. Japanese B encephalitis virus increased at a logarithmic rate for the first 72 hours. The virus concentration remained at maximal titre for the duration of the experiment. Symptoms were observable 96 to 120 hours after infection. 4. Western Equine encephalomyelitis virus grew at a logarithmic rate, even though a large inoculum was used. The maximal titre was achieved within 24 to 30 hours after inoculation. Generalized symptoms were evident by the 30 hour period and deaths were first noted at the 36 hour period. 5. Eastern Equine encephalomyelitis virus showed a logarithmic rate of increase during initial 24 hour after inoculation. Maximal virus persisted through onset of morbidity (30 hours) up to time of death (36 hours). The relations of phosphate metabolism in virus infected brain tissues to virus growth were examined: 1. St. Louis encephalitis virus. The relative specific activity of total acid-soluble phosphate was found to increase with the progress of infection. Analysis of this fractions showed that the ortho phosphate and total acid-soluble phosphate fractions had parallel activities which increased with, but lagged, the virus growth. The increased activity of the latter fraction was due to the changes in the ortho phosphate fraction. No evidence of a virus effect on the organic acid-soluble phosphates could be detected. 2. Japanese B encephalitis virus. Ortho and total acid-soluble phosphates were found to have increasing rates of turnover relative to, but lagging, the increase in virus concentration. 3. Eastern Equine encephalomyelitis. (a) Ortho and total acid-soluble phosphates were found to have increasing rates of turnover relative to, but lagging, the increase in virus concentration. (b) Virus-infected brain tissue was shown to be permeable to trypan blue dye, whereas non-infected brain tissue ere not. Infections with the viruses of eastern Equine encephalomyelitis, St Louis and Japanese B encephalitis were shown to increase the permeability of the blood-brain barrier to radioactive iodide. The increased permeability of the blood-brain to radioactive phosphate associated with virus infection could be simulated by a bacterial pyrogen. Both effects were suppressed by pre-treatment of the animals with cortisone which affected the R.S.A. of both the ortho and total acid-soluble phosphates. Cortisone treatment did not affect the rate of Eastern Equine encephalomyelitis virus production in infected mouse brain tissue. It was shown that the increased rate of phosphate turnover associated with virus growth was non-specific and evident of pathology (i.e., inflammation) rather than metabolism.