Studies on the entry of viruses into the central nervous system of mice via the circulation. Differential effects of vasoactive amines and CO2 on virus infectivity.

The inhalation of CO(2) exerted a selective action on the entry of viruses into the CNS of mice via the circulation. In 6 wk old animals, the infectivity of poliovirus, vaccinia, and vesicular stomatitis viruses was enhanced, whereas the entry of herpesviruses and of a neurotropic influenza virus was not affected. However, in 3 to 4 wk old mice, inhalation of the gas enhanced the infectivity of all the viruses. To explain the relationship of age to the animals' response to CO(2), it was proposed that CO(2) inhalation, by increasing the rate of cerebral blood flow, served to increase the exposure of some extraneural cell(s) to virus, possibly the cerebrovascular endothelial cell, in which virus replicated and reached the brain parenchyma by direct extension of the infectious process. Consequent to maturation, the postulated target cell developed resistance to certain viruses, while its susceptibility to others remained unchanged. Inoculation of adrenalin or serotonin simultaneously with virus into the circulation enhanced the CNS infectivity of all the viruses tested in both 4 wk and 6 wk age groups of mice. The enhancing effects were completely inhibited by the action of an alpha-adrenergic blocking agent; it was therefore concluded that hemodynamic changes produced by the contractile response of the smooth muscle cells in the vessel walls mediated the enhancing effect. It was suggested that a vasopressor response invoked in the peripheral vessels, with a consequent increase in cerebral blood flow, increased virus dosage to the CNS. In addition, a direct effect of the vasoactive amine on the cerebral vessels, resulting in the disruption of an anatomical "barrier", was considered as a contributory factor in increasing the transfer of virus to the CNS from the circulation.