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  • Review Article
  • Published:

Immunopathogenesis of coronavirus infections: implications for SARS

Nature Reviews Immunology volume 5, pages 917–927 (2005)Cite this article

Key Points

  • The severe acute respiratory syndrome (SARS), which was first identified in 2003, is caused by a novel coronavirus: the SARS coronavirus (SARS-CoV).

  • Many features of the infection indicate that an excessive, but perhaps 'normal', immune response contributes to SARS.

  • Several coronaviruses cause diseases that result in considerable morbidity and mortality in animals. Some of these diseases are also immune mediated and provide insights into the pathogenesis of SARS.

  • Feline infectious peritonitis virus (FIPV) causes a fatal, immune-mediated disease of felines. Macrophage infection, lymphocyte depletion and antibody-dependent disease enhancement are hallmarks of this disease.

  • Infection with the murine coronavirus murine hepatitis virus (MHV) strain JHM results in immune-mediated demyelination. Similar to SARS, macrophage activation is a key component in the pathogenic process.

  • Another strain of MHV, MHV-3, causes a fatal, fulminant hepatitis. MHV-3 infection of macrophages, with subsequent activation and induction of expression of a novel procoagulant, fibrinogen-like protein 2 (FGL2), is required for severe disease.

  • Chickens that are infected with avian infectious bronchitis virus (IBV) develop respiratory and renal disease. An excessive innate immune response contributes to the pathogenic process in these animals.

  • To develop effective therapies for SARS will require understanding of the contributions of direct injury by virus and of the host immune response to pathogenesis. This requires further studies of the interactions of SARS-CoV with its target cells and necessitates the development of an animal model that reproduces the pulmonary infection that is observed in infected humans.

Abstract

At the end of 2002, the first cases of severe acute respiratory syndrome (SARS) were reported, and in the following year, SARS resulted in considerable mortality and morbidity worldwide. SARS is caused by a novel species of coronavirus (SARS-CoV) and is the most severe coronavirus-mediated human disease that has been described so far. On the basis of similarities with other coronavirus infections, SARS might, in part, be immune mediated. As discussed in this Review, studies of animals that are infected with other coronaviruses indicate that excessive and sometimes dysregulated responses by macrophages and other pro-inflammatory cells might be particularly important in the pathogenesis of disease that is caused by infection with these viruses. It is hoped that lessons from such studies will help us to understand more about the pathogenesis of SARS in humans and to prevent or control outbreaks of SARS in the future.

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Figure 1: The severe-acute-respiratory-syndrome coronavirus genome and virion.
Figure 2: Macrophage infection and antibody-dependent enhancement of virus entry in infection with feline infectious peritonitis virus.
Figure 3: Mechanisms of immune-mediated demyelination in infection with murine hepatitis virus.
Figure 4: Infection with murine hepatitis virus strain 3 results in upregulation of expression of fibrinogen-like protein 2.

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Acknowledgements

We thank J. Harty, T. Gallagher, S. Varga and N. Butler for comments. This work was supported by the National Institutes of Health (United States) and the National Multiple Sclerosis Society (United States).

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Authors and Affiliations

  1. Interdisciplinary Program in Immunology, University of Iowa, Iowa City, 52242, Iowa, USA

    Ajai A. Dandekar & Stanley Perlman

  2. Departments of Pediatrics University of Iowa, Iowa City, 52242, Iowa, USA

    Stanley Perlman

  3. Microbiology, University of Iowa, Iowa City, 52242, Iowa, USA

    Stanley Perlman

Authors
  1. Ajai A. Dandekar
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  2. Stanley Perlman
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Correspondence to Stanley Perlman.

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DATABASES

Entrez Gene

ACE2

CCL2

CD66

CXCL8

CXCL10

FGL2

IL-6

IRF3

p38MAPK

spike

Infectious diseases information

SARS

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Glossary

HAEMOPHAGOCYTOSIS

The phagocytosis of erythrocytes that results from excessive activation of macrophages. This is usually a consequence of uncontrolled activation and proliferation of T cells.

MOLECULAR MIMICRY

A mechanism for the induction of autoimmunity in which a pathogen expresses a protein or peptide that is similar to a self-protein. After the induction of a pathogen-specific immune response, a crossreactive response to self results in autoimmune pathology.

EPITOPE SPREADING

The de novo activation of autoreactive T cells by self-antigens that have been released after virus-specific T- or B-cell-mediated bystander damage.

ENZOOTIC VIRUS

A virus that infects animals and is endemic to a geographical locale, with only minimal changes in its incidence over time.

ABORTIVE INFECTION

An infection in which viral replication is initiated but no infectious virus is produced.

SEROSITIS

Inflammation of the membranes that line the lungs (the pleura), the heart (the pericardium), and the abdomen (the peritoneum) and the organs within.

PYOGRANULOMATOUS VASCULITIS

A type of vasculitis (that is, inflammation of the blood vessels) that is associated with a chronic inflammatory process in which neutrophils are mixed with components of granulomas.

ASCITIC FLUID

Serous fluid that accumulates in the abdominal cavity. It might result from serositis.

GRANULOMA

A collection of modified macrophages that resemble epithelial cells. This is usually surrounded by a layer of lymphocytes that often includes multinucleated giant cells. Granuloma formation is a chronic inflammatory response that is initiated by various infectious and non-infectious agents.

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Dandekar, A., Perlman, S. Immunopathogenesis of coronavirus infections: implications for SARS. Nat Rev Immunol 5, 917–927 (2005). https://doi.org/10.1038/nri1732

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