Cell-mediated cytotoxicity in recovery from poxvirus infections.
The availability of mutant and gene targeted knockout mice with defects in components of cellular cytotoxicity mediated by either the Fas or the exocytosis pathway permitted an analysis of their role in recovery from poxvirus infections. Ectromelia (EV), a natural mouse pathogen causing mousepox, the closely related orthopoxviruses cow pox (CPV) and vaccinia virus (VV), each encode serpins that inhibit Fas mediated apoptosis and lysis of target cells. Nevertheless, distinct differences were seen when the three viruses were inoculated into perforin-deficient mice: highly resistant C57Bl/6 mice became susceptible to low doses of EV; resistance to CPV increased whereas there was no effect on VV infections. Absence of the cytolytic granule associated granzymes (gzm) A and B rendered C57Bl/6 mice increasingly more susceptible to EV infections. Lack of both gzms rendered them as susceptible as perforin deficient mice, despite the presence of functionally active perforin. Elevated EV titres in liver and spleen of gzmA x B deficient mice, early after infection and before cytotoxic T cells were detectable, strongly suggests that these two gzms exert an antiviral effect by a mechanism distinct from effector molecules of NK and cytotoxic T cells.
Müllbacher
Arno
A
Division of Immunology and Genetics, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra, ACT 2601, Australia. arno.mullbacher@anu.edu.au
D000818:Animals; D015608:Cowpox virus / Q000276:immunology / Q000472:pathogenicity; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D004481:Ectromelia virus / Q000276:immunology / Q000472:pathogenicity; D005089:Exocytosis / Q000276:immunology; D053804:Granzymes; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011213:Poxviridae Infections / Q000201:enzymology / Q000276:immunology* / Q000821:virology; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology / Q000472:pathogenicity; D019014:fas Receptor / Q000276:immunology
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases