Culture filtrates of Proteus mirabilis contain a viral inhibitory substance (VIS) which has a selective action. It inhibits the plaque formation by Sindbis and vesicular stomatitis viruses in chick embryo cell cultures without parallel depression of viral yield or cytopathogenic effect in cultures maintained in fluid medium.The action of VIS is both time- and temperature-dependent. The inhibitor does not affect viral replication or degenerative changes produced by vaccinia, polio 1, echo 11, and coxsackie A9 viruses in tube cultures.The action of VIS is intracellular. It is not caused by direct inactivation of viral infectivity, by cytotoxicity, by impairment of viral adsorption properties of cells, or by interference with the process of virus release. Furthermore, the action of VIS is mediated by a mechanism other than the induction of interferon.The inhibitor is a soluble non-dialyzable substance. It is thermostable at 60 °C for 1 h but is labile when stored at either 4 °C or −20 °C for periods more than 3 weeks. Neither ultraviolet irradiation nor treatment with trypsin affects VIS activity. The antiviral action is destroyed by either 0.1 M potassium periodate or dialysis against pH 2 buffer.Other members of the Proteus group produced substance(s) that inhibited Sindbis virus plaque formation. Such inhibitors have not been characterized.Principles such as VIS may serve as models of inhibitors which are selectively active against in vitro localized viral lesions.
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