Evidence that NK cells and interferon are required for genetic resistance to lethal infection with ectromelia virus.
C 57 BL/6 mice developed resistance to lethal intravenous challenge with virulent (Moscow strain) ectromelia virus between 2 and 3 weeks of age. The fraction of C57 BL/6 mice in which virus was detected in spleen was significantly lower than for DBA/2 mice by day 3. Thereafter, C 57 BL/6 mice had significantly reduced virus titers in spleen compared with those of DBA/2 mice. Resistance was abrogated by treatment with anti-asialo GM1 gammaglobulin, which blocks NK cell activity, or with anti-interferon (IFN) alpha, beta. C 57 BL/6 mice carrying the bg/bg mutation, associated with a deficiency of NK cells, were highly susceptible to lethal infection as were athymic mice derived from a resistant genetic background. Virus titers in spleens of C 57 BL/6 mice treated with anti-asialo GM1 or anti-IFN alpha, beta were significantly higher 4 days after virus challenge than were titers in C 57 BL/6 mice treated with normal rabbit serum. The results strongly suggest that genetic resistance to lethal ectromelia virus infection requires non-specific host defenses such as NK cells and IFN alpha, beta that are activated during the first 3 to 4 days of infection.
Jacoby
R O
RO
Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut.
Bhatt
P N
PN
Brownstein
D G
DG
D000375:Aging / Q000276:immunology; D000818:Animals; D004481:Ectromelia virus / Q000276:immunology / Q000302:isolation & purification; D004482:Ectromelia, Infectious / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate / Q000235:genetics; D007372:Interferons / Q000502:physiology*; D007694:Killer Cells, Natural / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D013154:Spleen / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology; D005719:gamma-Globulins / Q000008:administration & dosage / Q000276:immunology
D005719:gamma-Globulins; D007372:Interferons