Measles virus giant cell inducing factor (fusion factor)

Abstract

Treatment of a line of human amnion cells (AV3) with high titers of measles virus resulted in a rapid sequence of morphological alterations. Cell limits became less distinct within 30 minutes, and cytoplasmic fusion was complete within 5 hours. Measles virus rendered incapable of replication by irradiation with ultraviolet light retained the ability to induce these changes. The activity associated with untreated or ultraviolet inactivated measles virus which induces the rapid (within 5 hours) fusion of cultured cells has been termed fusion factor (FF). The cellular changes which occurred beyond 5 hours were studied employing measles virus inactivated by ultraviolet irradiation. Nuclear alterations induced by FF were related to the mitotic cycle. Interphase nuclei appeared to be unaffected, while nuclei undergoing mitosis developed aberrant forms. Nuclear events within individual syncytia were synchronized. The nuclear changes consisted of aggregation of chromatin, disappearance of nuclear membranes, central clumping of chromatin of adjacent nuclei, and finally condensation of cytoplasm around the mass of disordered nuclear material. Based upon studies of parameters affecting the fusion process, an assay was developed in which monolayers of AV3 cells were exposed to measles preparations at a temperature of 36°, pH 8.3, for 5 hours. The infectivity: FF ratios of measles virus pools averaged 10 5.8. The attachment of FF to the cell membrane at 36° required an incubation time and in part remained accessible to antiserum neutralization or reversal for a period after attachment. There was a marked cellular specificity of FF activity. Human epithelial lines, AV3, WS, HeLa, KB, HEp-2, intestine (Henle), conjunctiva (Chang), and some sublines of Detroit-6 were sensitive to FF. The Attleson diploid epithelial line was insensitive. Human diploid fibroblasts (MAF) did not fuse, but underwent a “stringy degeneration.” Primary human cells and continuous and primary cells of monkey and lower animals were insensitive.