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

Despite initial virus control by CD8(+) cytotoxic T lymphocytes (CTLs), non cytopathic or variably cytopathic viruses (e.g., hepatitis B and C viruses, HIV) are able to establish persistent infections. The role of neutralizing antibodies (nAbs) in controlling disease progression is unclear. Therefore , the phenomenon of viral evasion from the nAb response and its implication s for virus persistence remain controversial. Here we demonstrate nab-media ted viral clearance in CTL-deficient mice infected with the prototypic nonc ytopathic lymphocytic choriomeningitis virus (strain WE). During prolonged CTL absence, neutralization-resistant virus mutants were selected in indivi dual mice within 70-90 days. In naive animals infected with these virus var iants only low nAb responses were induced, resulting in an increased tenden cy of virus to persist.