Methods for Monitoring in the Environment
Methods for Measuring Human Exposure
Strategies for Preventing or Controlling Exposure
Absorption, Distribution and Metabolism
Sites of Toxicity
Biomarkers of Disease
Molecular Mechanisms of Action
SARS is caused by SARS-CoV, a virus belonging to the coronavirus family. Viruses are toxic because they invade and eventually kill host cells in order to survive and replicate. SARS is primarily transmitted by close person to person contact which results in the deposition of infected respiratory droplets on the mucous membranes of the mouth, nose or eyes. The coronavirus particles contained in these droplets will invade epithelial cells of the mucosal lining, replicate using the host cell synthetic machinery and ultimately release new virus particles that will invade new cells. This process leaves the infected host cells to rupture and die.
The immune system attempts to fight off viral infection using nonspecific immune defenses (fever, inflammation), which aim to limit and control viral spread, and antigen specific immune responses (antibodies, T-cells). The goal of the immune response is to eliminate the virus and cells harboring the virus. In the effort to eliminate the source of new virus, cell mediated immunity (T-cells) will lyse and kill infected host cells. Therefore, not only do the viruses induce the toxic effect of host cell death, but the immune response induced by the host can also bring about toxic effects.
In the case of SARS, cell invasion spreads to and primarily occurs in the mucosal epithelium of the respiratory tract. Due to viral invasion of host cells and the immune response, SARS patients will experience symptoms of fever, headache and body aches, and as the infection progresses respiratory symptoms develop. The infected can suffer from pneumonia, hypoxia and respiratory failure. The outcome of infection depends on how effective the hosts immune system is in fighting off the virus. Failure to resolve SARS-CoV infection can lead to death of the patient.
The angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for SARS-CoV. This receptor is found in the lungs, heart, kidney and GI tract with the lung and kidney being the primary sites of expression. The tissue distribution of ACE2 is concordant with the pathology of SARS. The major effects of SARS are seen in the lungs but SARS-CoV has also been found in kidney tissue of infected patients. Furthermore, viral replication has been observed in the small and large intestine, which can explain the occasional gastrointestinal sypmtoms associated with some patients. The function of ACE2 is to regulate cardiac function but it is uncertain if ACE2 enzymatic activity is disrupted by SARS-CoV in a manner that contributes to the pathogenesis of SARS.
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