33 A Mitotic Inhibitor Produced by Rubella Virus Infection of Human Fibroblasts

Abstract

When infected with rubella virus, many human diploid fibroblast cell strains show mild to marked degrees of mitotic inhibition (PLOTKIN et al.: Amer.J. Epidem. 81: 71 [1965]); cell strains derived from infected fetuses divide more slowly than normal (RAWLS and MELNICK: J.exp.Med. 123: 795 [1966]); and infants congenitally infected with rubella show mitotic inhibition and growth retardation (NAEYE and BLANC : J.amer.med. Ass. 194: 1277 [1965]). In seeking an explanation for these phenomena a substance inhibiting mitosis was found in infected WI-38 cells. WI-38 cells that had gone into mitotic arrest two weeks after rubella virus infection were extracted by freeze-thawing. When freed of virus, extracts of infected cells induced mitotic inhibition of normal WI-38 cells and of a skin fibroblast cell strain. No effect was seen on continuous lines of human cells or on non-human cell lines. The inhibitory substance was trypsin-sensitive and heatlabile but was unaffected by rubella antibody, ether, ribonuclease, or deoxyribonuclease. It was not sedimentable or acid-stable and did not protect cells against the action of vesicular stomatitis virus. Concentrated rubella virus inactivated by ultra-violet irradiation did not itself produce growth inhibition. This substance offers a potential explanation for the mitotic inhibition associated with rubella virus infection in vitro and in vivo. (SPR)