Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells

Viruses that are non- or poorly cytopathic have developed various strategies to avoid elimination by the immune system and to persist in the host^1-3. Acute infection of adult mice with the noncytopathic lymphocytic choriomeningitis virus (LCMV) normally induces a protective cytotoxic T-cell response that also causes immunopathology^4-7. But some LCMV strains (such as DOCILE⁸ (LCMV-D) or Cl-13 Armstrong (Cl-13) ⁹) derived from virus carrier mice tend to persist after acute infection of adult mice without causing lethal immunopathological disease^4,5. Tendency to persist correlates with tropism ^8,10, rapidity of virus spread⁸ and virus mutations ^11,12. We report here that these LCMV isolates may persist because they induce most of the specific antiviral CD8⁺ cytotoxic T cells so completely that they all disappear within a few days and therefore neither eliminate the virus nor cause lethal immunopathology. The results illustrate that partially and sequen-tially induced (protective) immunity or complete exhaustion of T-cell immunity (high zone tolerance) are quantitatively different points on the scale of immunity; some viruses exploit the latter possibility to persist in an immunocompetent host.