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

Journal article

Despite initial virus control by CD8(+) cytotoxic T lymphocytes (CTLs), noncytopathic 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 implications for virus persistence remain controversial. Here we demonstrate nAb-mediated viral clearance in CTL-deficient mice infected with the prototypic noncytopathic 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.

Authors: Ciurea, A; Klenerman, P; Hunziker, L; Horvath, E; Senn, B

• Publication status: Published
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 97
• Issue: 6
• Pages: 2749-2754
• Publication date: 2000-03-01
• DOI: 10.1073/pnas.040558797
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Animals; Mice, Inbred BALB C; Mice; Antigens, CD8; Antibodies, Viral; Antibodies, Monoclonal; Time Factors; Lymphocytic choriomeningitis virus; Spleen; Point Mutation; T-Lymphocytes, Cytotoxic; Lung; Mice, Inbred C57BL; CD8-Positive T-Lymphocytes; Lymphocytic Choriomeningitis