Simian virus 40-permissive cell interactions: selection and characterization of spontaneously arising monkey cells that are resistant to simian virus 40 infection

Abstract

A fraction of permissive African green monkey kidney CV1 cells survive SV40 infection. The frequency of such surviving cells depends only upon the concentration of infecting virus, parental and progeny, to which the cells are exposed during the course of selection. Surviving clones, which can be freed of virus by cloning in the presence of SV40 antiserum, are indistinguishable from parental cells in their growth characteristics and display no SV40 T antigen; thus they are not transformed. Most surviving clones are < 10% as susceptible as parental cells to SV40 infection; 5-10% are < 1% as susceptible. None of these SV40-resistant clones is absolutely resistant to SV40 infection. Analysis of 16 independently arising resistant clones indicates that they all block SV40 infection at an early stage after adsorption and eclipse but before full uncoating. Viral mutants were isolated that partially overcome the block to infection in these cells; these host range viruses plaque on resistant lines 5-fold more efficiently than wild-type SV40 and have a characteristic plaque morphology. Fluctuation analysis indicates that resistant cells arise spontaneously during the growth of normally susceptible permissive cells. SV40-resistant cells are selected for, not induced by, SV40 infection.