Enveloped virus acquires membrane defect when passaged in fibroblasts from I-cell disease patients

Sindbis virus obtained after passage on human fibroblasts from patients with I-cell disease (mucolipidosis II) and called I-cell virus differed from Sindbis virus obtained from chick fibroblasts or from normal human fibroblasts in two ways: (1) The I-cell virus was extremely unstable to freezing and thawing, (2) The I-cell virus showed greatly exaggerated sensitivity to inactivation by Triton X-100. Sindbis virus from fibroblasts from two patients with mucolipidosis III, a milder form of I-cell disease, showed similar, though milder, freeze-sensitivity. When freeze-sensitive I-cell virus was passaged once in mouse L-cells or normal human fibroblasts, the virus was no longer abnormal. The viral glycoproteins of I-cell virus were not distinguishable from viral glycoproteins of controls by sodium dodecyl sulfate gel electrophoresis. Gel filtration of the glycopeptides suggested small differences in two of the four glycopeptides. These findings indicate that Sindbis virus is phenotypically altered when grown on I-cell fibroblasts. These alterations must be attributed to viral envelope components derived from the host plasma membrane (membrane lipids) or to alterations in viral envelope glycoproteins. In either case, the alterations appear related to the genetic defect in I-cell fibroblasts. From these results it is clear that enveloped viruses can be useful to demonstrate and to analyze membrane defects in certain human diseases. The phenotypically altered viruses may, in turn, provide probes for studying the functional relationships of virus membrane components.