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

Dimitrios Moskofidis, Franziska Lechner, Hanspeter Pircher, Rolf M. Zinkernagel

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915 Scopus citations


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) 9) 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 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.

Original languageEnglish (US)
Pages (from-to)758-761
Number of pages4
Issue number6422
StatePublished - Jan 1 1993
Externally publishedYes


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