ROLE OF VIRUS AND HOST VARIABLES IN VIRUS PERSISTENCE OR IMMUNOPATHOLOGICAL DISEASE CAUSED BY A NONCYTOLYTIC VIRUS

C57BL/6 mice infected with increasing doses of the Armstrong isolate of lymphocytic choriomeningitis virus (LCMV) or a variant Cl 13-Armstrong, derived from LCMV-Armstrong, exhibited distinct phenotypes with respect to clearance of virus and to cytotoxic CD8(+) T cell (CTL)-dependent immunopathological disease. Low (10(2) p.f.u.) and high doses (10(7) p.f.u.) of LCMV-Armstrong were cleared rapidly from immunocompetent mice. Inoculation of a high dose (10(7) p.fu.) of LCMV Cl 13-Armstrong temporarily induced a partial deletion of the antiviral CTL precursors (CTL-p) leading to chronic infection in several organs. Although virus was cleared from most organs by day 90-150 post-infection, it persisted in the kidney. The few remaining CTL-p were able to expand and eventually clear the virus. Systemic viral titres correlated inversely with the number of CTL-p. However, in contrast LCMV-Docile injected at high dose was able to cause complete exhaustion of CTL-p resulting in long term viral persistence. LCMV-Aggressive, derived from the same parental LCMV-WE (UBC) as Docile, showed a phenotype comparable to wild-type virus. Doses of < 10(7) p.fu. of both Armstrong virus and of Cl 13-Armstrong failed to exhaust CTL-p