Role of temperature-sensitive mutants in persistent infections initiated with vesicular stomatitis virus.
Noncytocidal persistent infections at 37 C of mouse L cells (Lvsv) with infective B particles of vesicular stomatitis virus (VSV) could be established only in the presence of large numbers of defective interfering (DI) particles. Under these conditions, there was a rapid spontaneous selection of temperature-sensitive (ts) virus. At 10 days there was an increase to 17.8% in the frequency of ts clones in the virus population; by 17 days this frequency had reached 85.2%, and by 63 days 100% of the clones isolated were ts at 39.5 C, the nonpermissive temperature used. All 34 of the clones isolated from the 84-day fluid had an RNA-phenotype, and 8 clones that were tested all belonged to VSV complementation group I. When tested by an interference assay, Lvsv fluids did not contain significant numbers of DI particles (less than 1 DI/PFU). Furthermore, persistent infection of L cells at 37 C could be initiated under conditions in which few, if any, DI particles were present by using low input multiplicities (10(-4) and 10(-5) of a clonal isolate of an RNA-group I mutant obtained from Lvsv cells. On the basis of these and other results, a mechanism is proposed to explain the role of ts mutants in both the establishment and maintenance of the persistently infected state.
D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division; D003561:Cytarabine / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral; D003609:Dactinomycin / Q000494:pharmacology; D003673:Defective Viruses / Q000254:growth & development; D005816:Genetic Complementation Test; D007739:L Cells; D008937:Mitomycins / Q000494:pharmacology; D009154:Mutation; D013696:Temperature; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development* / Q000302:isolation & purification; D014762:Viral Interference; D014779:Virus Replication / Q000187:drug effects
D008937:Mitomycins; D003561:Cytarabine; D003609:Dactinomycin; D001973:Bromodeoxyuridine