An essential role for type 1 interferon-gamma in terminating persistent viral infection.
The mechanism(s) by which infectious material is cleared by the host is an area of intensive study. This is especially so with the realization that persistent viral infection is a cause of chronic disease in humans and presents a major health problem. We have used the murine model of infection with lymphocytic choriomeningitis virus to evaluate immune clearance. Mice with a targeted disruption of the IFN-gamma gene mount effective cytotoxic T lymphocyte (CTL) responses after an acute viral challenge and clear virus. CD4+ T cells are not required but CD8+ T cells are mandatory. In contrast, CTL from mice with targeted disruption of the IFN-gamma gene are unable to clear virus from persistently infected mice. In addition to the requirement for IFN-gamma, CD4+ T cells are essential for maintaining a CD8(+)-mediated cure of persistent viral infection.
Tishon
A
A
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Lewicki
H
H
Rall
G
G
Von Herrath
M
M
Oldstone
M B
MB
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000382:microbiology*; D002908:Chronic Disease; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000502:physiology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012367:RNA, Viral / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D012367:RNA, Viral; D007371:Interferon-gamma