Characterization of human cells persistently infected with cytomegalovirus and exposed to a chemical carcinogen.
A non-productive, persistent human cytomegalovirus (CMV) infection was developed in human embryo lung (LU) cells by initially using supraoptimal temperatures to restrict the replication of a recent CMB isolate (76-24). Although CMV replication was observed in some cells within a few weeks of shifting the cultures to 37 degrees C and subculturing, CMV cytopathic effects and infectious CMV were not detected with further subculturing during the next 5 weeks. CMV-specific nuclear antigens were, however, observed in most cells (designated LU-76-24) for 38 additional culture passages made during the following 12 months. Although the LU-76-24 cells were morphologically distinct from LU cell cultures carried in parallel as controls, the LU-76-24 were contact-inhibited in spite of a somewhat disoriented growth pattern. Treatment of LU-76-24 cells with 0.05 microgram/ml of the chemical carcinogen 4-nitroquinoline 1 oxide (NQO) induced a lytic CMV infection from which a clone of cells (designated LUC-NQO) was isolated. No effect was seen when LU cells were treated with the same dose of NQO. LUC-NQO cells were morphologically altered from LU-76-24 cells and had lost contact inhibition. Even though CMV-specific nuclear antigens were observed in LUC-NQO cells, infectious CMV was not detected in lysates of these cells, nor was CMV rescued by co-cultivation of these cells with susceptible cells or by induction with 5-iodo-2'-deoxyuridine. LUC-NQO, but not LU or LU-76-24 cells, plated with good efficiency in semi-solid medium. The results indicate that long-term, non-productive, persistent CMV infections can be established in vitro and suggest that such cells may be more susceptible than non-infected cells to the action of chemical carcinogens.
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D000956:Antigens, Viral / Q000032:analysis; D002273:Carcinogens / Q000494:pharmacology*; D002460:Cell Line; D003260:Contact Inhibition; D003587:Cytomegalovirus / Q000254:growth & development* / Q000276:immunology / Q000302:isolation & purification; D004622:Embryo, Mammalian; D005455:Fluorescent Antibody Technique; D006801:Humans; D008168:Lung; D013997:Time Factors; D014776:Virus Cultivation; D014779:Virus Replication / Q000187:drug effects
D000956:Antigens, Viral; D002273:Carcinogens; D015112:4-Nitroquinoline-1-oxide