Apoptosis mediated by Fas but not tumor necrosis factor receptor 1 prevents chronic disease in mice infected with murine cytomegalovirus

Academic Article

Abstract

  • The role of Fas- and TNF-receptor 1 (TNF-R1)-mediated apoptosis in the clearance of virally infected cells and in the regulation of the immune response was analyzed after murine cytomegalovirus (MCMV) infection of C57BL/6 (B6)-+/+ mice, Fas-mutant B6-lpr/lpr mice, TNF-R1 knockout B6- tnfr(0/0) mice, and double-deficient B6-tnfr(0/0) lpr/lpr mice. There was approximately equivalent clearance of MCMV in B6-+/+, B6-tnfr(0/0), and B6- lpr/lpr mice, and by day 28 no infectious virus could be detected in the liver, kidney, lung, or peritoneal exudate. However, delayed virus clearance was observed in B6-tnfr(0/0) lpr/lpr mice. An acute inflammatory response occurred in the liver, lung, and kidney of all mice, which was most severe 7 d after MCMV infection, but resolved by day 28 in B6-+/+ and B6-tnfr(0/0) mice, but not in B6-lpr/lpr or B6-tnfr(0/0) lpr/lpr mice. These results indicate that apoptosis mediated by either Fas or TNF-R1 is sufficient for rapid clearance of the virus. However, apoptosis induced by Fas, but not TNF- R1, is required for the downmodulation of the immune response to the virus and prevention of a chronic inflammatory reaction.
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    Author List

  • Fleck M; Kern ER; Zhou T; Podlech J; Wintersberger W; Edwards CK; Mountz JD
  • Start Page

  • 1431
  • End Page

  • 1443
  • Volume

  • 102
  • Issue

  • 7