Role of temperature-sensitive mutants in persistent infections initiated with vesicular stomatitis virus

Abstract

Noncytocidal persistent infections at 37.degree. C of mouse L [fibroblast] 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 reached 85.2%, and by 63 days 100% of the clones isolated were ts at 39.5.degree. C, the nonpermissive temperature used. All 34 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 (< 1 DI/PFU [plaque forming unit]). Persistent infection of L cells at 37.degree. 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. A mechanism is proposed to explain the role of ts mutants in the establishment and maintenance of the persistently infected state.