Non-Specific Viral Inactivating Substance (Vis) in Human and Mammalian Sera

Summary

The heat-labile viral inactivating substance (VIS) against Newcastle disease virus (NDV) was studied in human and rabbit sera.

Four procedures for the inhibition of VIS were demonstrated, namely treatment with 1) trypsin, 2) streptokinase, 3) ethylenediamine-tetraacetate, and 4) tissues. The inhibition of VIS by streptokinase appeared to be effected by the conversion of plasminogen to its active form, plasmin. The temperature sensitivity of VIS and the enzymatic destruction of VIS by trypsin and streptokinase indicate that VIS activity depends upon the integrity of a labile serum protein. Tissue inhibition of VIS was greatest in the kidney, moderate in spleen, brain, lung, liver and chick embryo, less in muscle, and minimal or entirely absent in red blood cells and extraembryonic fluids of the chick embryo. The VIS inhibitor in tissues was found associated with the nuclear, mitochondrial and microsomal fractions.

Destruction of VIS by the above inhibitors failed to release infectious virus after the VIS-virus union had taken place. Also, dilution of a “neutral” mixture of virus and VIS, or addition thereto of large amounts of inactive virus, failed to reactivate virus in either instance. Thus the present data indicate that the virus is irreversibly inactivated by VIS. In this respect, the union of NDV with VIS appears to be fundamentally different from the binding of NDV by specific antibody. Serum VIS directed against NDV was further found to differ significantly from another nonspecific viral inhibitor, the β inhibitor of influenzal infectivity.

Based upon the existence of circulating VIS, serum proteases which potentially may alter the level of VIS, and an intracellular inhibitor of VIS, a system of “species” or “natural” resistance to NDV is postulated.