The Immunobiology of SARS

Abstract

Severe acute respiratory syndrome (SARS) presented as an atypical pneumonia that progressed to acute respiratory distress syndrome in approximately 20% of cases and was associated with a mortality of about 10%. The etiological agent was a novel coronavirus (CoV). Angiotensin-converting enzyme 2 is the functional receptor for SARS-CoV; DC-SIGN and CD209L (L-SIGN) can enhance viral entry. Although the virus infects the lungs, gastrointestinal tract, liver, and kidneys, the disease is limited to the lungs, where diffuse alveolar damage is accompanied by a disproportionately sparse inflammatory infiltrate. Pro-inflammatory cytokines and chemokines, particularly IP-10, IL-8, and MCP-1, are elevated in the lungs and peripheral blood, but there is an unusual lack of an antiviral interferon (IFN) response. The virus is susceptible to exogenous type I IFN but suppresses the induction of IFN. Innate immunity is important for viral clearance in the mouse model. Virus-specific neutralizing antibodies that develop during convalescence prevent reinfection in animal models.

Lung Cell Tropism and Inflammatory Cytokine-Profile of Porcine Respiratory Coronavirus Infection

“…PRCV infection in pigs has previously been suggested as a good model for studying the effect of corticosteroids on severe acute respiratory syndrome coronavirus (SARS-CoV) infection in humans [46]. Chen and Subbarao have done an extensive summary on currently available knowledge of SARS immunobiology [47]. Despite the fact that SARS-CoV causes severe illness in humans and is lethal in 10% of the cases, in contrast to PRCV in pigs, which is usually mild or subclinical, there are some similarities between the courses of these two infections.…”

“…Both PRCV and SARS-CoV seem to target predominantly type 2 pneumocytes in the lungs [50,51]. Conflicting reports on the ability of SARS-CoV to infect macrophages have been discussed in the above mentioned review article [47]. There is still very limited information about the induction of cytokines by SARS-CoV in the lungs of humans.…”

“…There is still very limited information about the induction of cytokines by SARS-CoV in the lungs of humans. However, the fact that cytokines have been found in sera from SARS patients during early stage of infection (reviewed in [47]) suggests that there may be enhanced cytokine production in the lungs as well. So far, the cytokine profiles in the lungs have been examined only in autopsy material from SARS patients that have died from acute respiratory distress at later stage of infection.…”

Milk Derived Peptides with Immune Stimulating Antiviral Properties

“…Although it has been identified that a metallopeptidase, angiotensin-converting enzyme 2, is a functional receptor for severe acute respiratory syndrome coronavirus infection [115], other reports have demonstrated that DC-SIGN, L-SIGN (also called CD209L, specific for liver/lymph node) [116][117][118][119], and heparan sulphate [120] also are involved in the virus pathogenesis. Thus, there are reasons to believe that lactoferrin could prevent severe acute respiratory syndrome coronavirus spread in the host through the same mechanism as described for human immunodeficiency virus, by interacting with DC-SIGN or heparan sulphate receptors.…”

“…A pentapeptide ( -casochemotide-1) with amino acid sequence (YPVEP) matching an actinase E digest peptide from bovinecasein (corresponding to fraction [114][115][116][117][118], has been tested and demonstrated to both chemoattract and activate, human and mouse monocytes and macrophages by using a unique G-protein coupled receptors [142].…”