Role of defective simian virus 40 genomes in establishment and maintenance of persistently infected primate cell lines.

Studies are reported of persistent simian virus 40 (SV40) infections of fully permissive monkey (TC-7 and BSC-1) and human (A172) cell lines, with emphasis on the role of viral defectives in establishment and maintenance of persistence. The presence of defectives prevented complete cell killing and allowed the establishment of persistently infected cultures. Hirt supernate DNAs from these cultures showed the continuing presence of defective genomes. Restriction enzyme analysis demonstrated that altered defective genomes evolved during passage of the carrier cultures, but that they always reflected structures of the genomes used to established the cultures. There was some host cell specificity in the effectiveness of establishment of persistence, e.g., TC-7-derived defectives were more effective in preventing killing of TC-7 than of BSC-1 or A172 cells. Persistent infections of TC-7 cells could also be established in the absence of defectives, but in the presence of neutralizing anti-SV40 antiserum. In fact, defectives were eliminated from carrier cultures established in the presence of antiserum. When antiserum was withdrawn, the wild-type SV40 grew and destroyed the cells. Antiserum maintains a low level of infection by neutralizing viruses outside the cells, so that many cells do not become infected. Defectives are eliminated because spread of infection is effectively at very low multiplicity. Carrier cultures that are established and maintained by defectives result from intracellular interference by the defectives with the normal development of wild-type virus.