Viral persistence in vivo through selection of neutralizing antibody-escape variants

摘要

Despite initial virus control by CD8+ cytotoxic T lymphocytes (CTLs), noncytopathic or variably cytopathic viruses (e.g., hepatitis B and C viruses, HlV) are able to establish persistent infections. The role of neutralizing antibodies (nAbs) in controlling disease pro- gression is unclear. Therefore, the phenomenon of viral evasion from the nAb response and its implications for virus persistence remain controversial. Here we demonstrate nAb-mediated viral clearance in CTL-deficient mice infected with the prototypic non- Cytopathic lymphocytic choriomeningitis virus (strain WE). During prolonged CTL absence. neutralization-resistant virus mutants were selected in individual mice within 70-90 days. In naive animals infected with these virus variants only low nAb responses were induced. resulting in an increased tendency of virus to persist.