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

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Abstract
VIRUSES that are non- or poorly cytopathic have developed various strategies to avoid elimination by the immune system and to persist in the host1-3. Acute infection of adult mice with the noncytopathic lymphocytic choriomeningitis virus (LCMV) normally induces a protective cytotoxic T-cell response that also causes immunopathology4-7. But some LCMV strains (such as DOCILE8 (LCMV-D) or Cl-13 Armstrong (Cl-13)) derived from virus carrier mice tend to persist after acute infection of adult mice without causing lethal immunopathological disease4,5. Tendency to persist correlates with tropism8,10, rapidity of virus spread8 and virus mutations11,12. 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 sequentially 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.