Molecular mimicry of ACTH in SARS - implications for corticosteroid treatment and prophylaxis

Med Hypotheses. 2004;63(5):855-62. doi: 10.1016/j.mehy.2004.04.009.


For a virus to survive and replicate in an organism, it must employ strategies to evade and misdirect the host's immune response. There is compelling evidence that the primary immunoevasive strategy utilized by the SARS virus, like influenza, is to inhibit its host's corticosteroid stress response. This is accomplished by viral expression of amino acid sequences that are molecular mimics of the host's adrenocorticotropin hormone (ACTH). When the host produces antibodies against these viral antigens, the antibodies also bind to the host's own ACTH, which limits the host's stress response by interfering with ACTH's ability to stimulate the secretion of corticosteroids. This inadequate corticosteroid response provokes symptoms as a result of a relative adrenocortical insufficiency. Treatment with corticosteroids can relieve the patient's symptoms of adrenocortical insufficiency and give them the corticosteroid levels needed to fight their infection. Similarly, by taking moderate daily doses of corticosteroids as a prophylactic, it may be possible to avoid clinical infection with SARS. If SARS's ACTH mimic strategy never has an opportunity to get started, SARS's ability to evade its host's immune system while its viral load is low will be significantly impaired. In this article, amino acid sequences from the SARS and influenza viruses representing likely homology to human ACTH are identified. Evidence demonstrating that ACTH autoantibodies are produced during influenza infection is also presented. Early treatment with corticosteroids should lower the dose necessary to counteract SARS's ACTH autoantibody mechanism. If corticosteroid treatment is delayed until inflammatory cytokine levels are causing serious injury, only high doses of corticosteroids are likely to be effective.

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage*
  • Adrenocorticotropic Hormone / chemistry
  • Adrenocorticotropic Hormone / immunology*
  • Antibiotic Prophylaxis / methods*
  • Disease Transmission, Infectious / prevention & control
  • Humans
  • Models, Immunological
  • Molecular Mimicry / drug effects
  • Molecular Mimicry / immunology*
  • SARS Virus / immunology*
  • Severe Acute Respiratory Syndrome / drug therapy
  • Severe Acute Respiratory Syndrome / immunology*
  • Severe Acute Respiratory Syndrome / prevention & control*
  • Severe Acute Respiratory Syndrome / virology
  • Viral Proteins / chemistry
  • Viral Proteins / immunology*


  • Adrenal Cortex Hormones
  • Viral Proteins
  • Adrenocorticotropic Hormone