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Reversal of virus-induced systemic shock and respiratory failure by blockade of the lymphotoxin pathway

Nature Medicine volume 5, pages 1370–1374 (1999)Cite this article

Abstract

At present, little is known about the pathogenesis of acute virus-induced shock and pulmonary failure. A chief impediment in understanding the underlying disease mechanisms and developing treatment strategies has been the lack of a suitable animal model. This study describes a mouse model of virus-induced systemic shock and respiratory distress, and shows that blockade of the lymphotoxin beta receptor pathway reverses the disease.

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Figure 1: Infection of NZB mice with LCMV-13 results in mortality.
Figure 2: Histological profile of LCMV-13 infection in NZB mice.
Figure 3: Blockade of the LTβR signaling pathways substantially improves survival rates among NZB mice infected with LCMV-13.
Figure 4: A single-dose treatment of lethally infected mice after establishment of viral infection leads to a significant increase (P = 0.
Figure 5: Blockade of the LTβR pathway results in a decrease in LCMV-13 specific CD8 T cells.
Figure 6: Depletion of CD8+ T cells, not CD4+ T cells, reverses the lethal effects of LCMV-13 infection in NZB mice.
Figure 7: Mice that survive LCMV-13 infection clear the virus infection and show no signs of disease pathology.

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Acknowledgements

We thank P. Greer and T. Ferebee for their technical assistance in generating and staining tissue sections, and E. Halloran for advice on statistical analysis. This work was funded in part by NIH grants AI09866, AI30048 and NS21496. All animals used in experiments described here were treated in accordance with Emory University's guidelines.

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Authors and Affiliations

  1. Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, 30322, Georgia, USA

    Maryann T. Puglielli, John D. Altman & Rafi Ahmed

  2. Biogen Incorporated, 14 Cambridge Center, Cambridge, 02142, Massachusetts, USA

    Jeffrey L. Browning

  3. Schering-Plough Research Institute, Lafayette, 07848, New Jersey, USA

    Avery W. Brewer

  4. Department of Pathology, Washington University School of Medicine, St. Louis, 63110, Missouri, USA

    Robert D. Schreiber

  5. Infectious Disease Pathology Activity, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, 30322, Georgia, USA

    Wun-Ju Shieh & Sherif R. Zaki

  6. Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, 92037, California, USA

    M.B.A. Oldstone

Authors
  1. Maryann T. Puglielli
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Correspondence to Rafi Ahmed.

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Puglielli, M., Browning, J., Brewer, A. et al. Reversal of virus-induced systemic shock and respiratory failure by blockade of the lymphotoxin pathway. Nat Med 5, 1370–1374 (1999). https://doi.org/10.1038/70938

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