Viral persistence in vivo through selection of neutralizing antibody-escape variants.
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.
Ciurea
A
A
Institute for Experimental Immunology, University Hospital, CH-8091 Zurich, Switzerland. aciurea@pathol.unizh.ch
Klenerman
P
P
Hunziker
L
L
Horvath
E
E
Senn
B M
BM
Ochsenbein
A F
AF
Hengartner
H
H
Zinkernagel
R M
RM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D008168:Lung / Q000276:immunology / Q000821:virology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017354:Point Mutation; D013154:Spleen / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D016827:CD8 Antigens