Summary
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 C 57 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) α, β. 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 α, β 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 α, β that are activated during the first 3 to 4 days of infection.
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Akagawa KS, Maruyama Y, Takano M et al. (1982) Appearance of a cell surface antigen expressed on mouse lung macrophages. Microbiol Immunol 25: 1215–1220
Bancroft GJ, Shellam GR, Chalmer JE (1981) Genetic influences on the augmentation of natural killer (NK) cells during murine cytomegalovirus infection: correlation with patterns of resistance. J Immunol 126: 988–994
Bhatt PN, Jacoby RO (1987) Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. I. Clinical responses. Lab Anim Sci 37: 11–15
Bhatt PN, Jacoby RO, Gras L (1988) Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. IV. Studies with the Moscow strain. Arch Virol 100: 221–230
Blanden RV (1970) Mechanisms of recovery from a generalized viral infection: mousepox. I. The effects of anti-thymocyte serum. J Exp Med 132: 1035–1054
Brownstein DG (1989) Failure of anti-asialo GM1 and the beige mutation to alter resistance to parainfluenza 1 (Sendai) virus pneumonia in mice. (In prep.)
Brownstein DG, Bhatt PN, Jacoby RO (1989) Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. V. Genetics of resistance to the Moscow strain. Arch Virol 107: 35–41
Bukowski JF, Woda BA, Habu S et al (1983) Natural killer cell depletion enhances virus synthesis and virus-induced hepatitis in vivo. J Immunol 131: 1531–1538
Bukowski JF, Woda BA, Welsh RM (1984) Pathogenesis of murine cytomegalovirus infection in natural killer cell-depleted mice. J Virol 52: 119–128
Doherty PC, Korngold R (1983) Characteristics of poxvirus-induced meningitis: virus-specific and non-specific cytotoxic effectors in the inflammatory exudate. Scand J Immunol 18: 1–7
Fenner F, Wittek R, Dumbell KR (1989) The orthopoxviruses. Academic Press, San Diego, pp. 269–302
Habu S, Hiroyasu F, Shimamura K et al (1981) In vivo effects of anti-asialo GM1 I. Reduction of NK activity and enhancement of transplanted tumor growth in nude mice. J Immunol 127: 34–38
Jacoby RO, Bhatt PN (1987) Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. II. Pathogenesis. Lab Anim Sci 37: 16–22
Jacoby RO, Bhatt PN, Johnson EA (1983) Pathogenesis of vaccinia (IHD-T) virus infection in BALB/cAnNCr mice. Lab Anim Sci 33: 435–441
Kasai M, Iwamori M, Nagai Y et al (1980) A glycolipid on the surface of mouse natural killer cells. Eur J Immunol 10: 175–180
Kawase ID, Urdel L, Brooks CG et al (1982) Selective depletion of NK cell activity in vivo and its effects on the growth of NK-sensitive and NK-resistant tumor cell variants. Int J Cancer 29: 567–574
Kees U, Blanden RV (1976) A single genetic element in H-2 K affects mouse T-cell anti-viral function in poxvirus infection. J Exp Med 143: 450–476
Kiessling R, Klein E, Pross H et al (1975) “Natural” killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cells. Eur J Immunol 5: 117–121
McKinnon KP, Hale AH, Ruebush MJ (1981) Elicitation of natural killer cells in beige mice by infection with vesicular stomatitis virus. Infect Immun 32: 204–210
Mims CA, White DO (1984) Viral pathogenesis and immunology. Blackwell, Oxford, pp 191–193
O'Neill HC, Blanden RV (1983) Mechanisms determining innate resistance to ectromelia virus infection in C 57 BL mice. Infect Immun 41: 1391–1394
O'Neill HC, Blanden RV, O'Neill TJ (1983) H-2-linked control of resistance to ectromelia virus infection in B 10 congenic mice. Immunogenetics 18: 255–265
O'Neill HC, Brenan M (1987) A role for early cytotoxic T cells in resistance to ectromelia virus infection in mice. J Gen Virol 68: 2669–2673
Shellam GR, Allan JE, Papadimitrou JM et al. (1981) Increased susceptibility to cytomegalovirus infection in beige mutant mice. Proc Natl Acad Sci USA 75: 5104–5108
Stanton GJ, Jordan C, Hart A et al. (1987) Nondetectable levels of interferon gamma is a critical host defense during the first day of herpes simplex virus infection. Microbiol Pathol 3: 179–183
Steel RGD, Torrie JH (1980) Principles and procedures of statistics, 2nd edn. McGraw-Hill, New York, pp 539–540, 544–545
Stein-Streilein J, Guffee J (1986) In vivo treatment of mice and hamsters with antibodies to asialo GM1 increases morbidity and mortality to pulmonary influenza infection. J Immunol 136: 1435–1441
Suzuki R, Suzuki N, Ebina N (1985) Suppression of alloimmune cytotoxic T lymphocyte (CTL) generation by depletion of NK cells and restoration of interferon and/or interleukin 2. J Immunol 134: 2139–2148
Tardieu M, Hery C, Dupuy JM (1980) Neonatal susceptibility to MHV 3 infection in mice II. Role of natural effector marrow cells in transfer of resistance. J Immunol 124: 418–423
Wallace GD, Buller RML, Morse HC III (1985) Genetic determinants of resistance to ectromelia (mousepox) virus-induced mortality. J Virol 55: 890–891
Welsh RM (1978) Mouse natural killer cells: induction, specificity, and function. J Immunol 121: 1631–1635
Welsh RM (1984) natural killer cells and interferon. CRC Crit Rev Immunol 5: 55–93
Welsh RM (1986) Regulation of virus infections by natural killer cells. Nat Immun Cell Growth Regul 5: 169–199
Welsh RM, Hallenbeck LA (1980) Effect of virus infections on target cell susceptibility to natural killer cell-mediated lysis. J Immunol 124: 2491–2497
Welsh RM, Kiessling RW (1980) Natural killer cell response to lymphocytic choriomeningitis virus in beige mice. Scand J Immunol 11: 363–367
Welsh RM, Zinkernagel RM, Hallenbeck LA (1979) Cytotoxic cells induced during lymphocytic choriomeningitis infection of mice. II. Specificities of the natural killer cells. J Immunol 122: 475–481
Yang H, Yogeeswaran G, Bukowski JF (1985) Expression of asialo GM1 and other antigens and glycolipids on NK cells and spleen leukocytes in virus-infected mice. Nat Immun Cell Growth Regul 4: 21–39
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Jacoby, R.O., Bhatt, P.N. & Brownstein, D.G. Evidence that NK cells and interferon are required for genetic resistance to lethal infection with ectromelia virus. Archives of Virology 108, 49–58 (1989). https://doi.org/10.1007/BF01313742
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DOI: https://doi.org/10.1007/BF01313742