Pathogenesis of severe acute respiratory syndrome

Abstract

Severe acute respiratory syndrome (SARS) is a zoonotic infectious disease caused by a novel coronavirus (CoV). The tissue tropism of SARS-CoV includes not only the lung, but also the gastrointestinal tract, kidney and liver. Angiotensin-converting enzyme 2 (ACE2), the C-type lectin CD209L (also known L-SIGN), and DC-SIGN bind SARS-CoV, but ACE2 appears to be the key functional receptor for the virus. There is a prominent innate immune response to SARS-CoV infection, including acute-phase proteins, chemokines, inflammatory cytokines and C-type lectins such as mannose-binding lectin, which plays a protective role against SARS. By contrast there may be a lack of type 1 interferon response. Moreover, lymphopenia with decreased numbers of CD4+ and CD8+ T cells is common during the acute phase. Convalescent patients have IgG-class neutralizing antibodies that recognize amino acids 441-700 of the spike protein (S protein) as the major epitope.

Figure 1

The SARS coronavirus. (a) Wet markets are the interface where animal to human inter-species transmission of SARS-CoV occurred. Guangzhou government officers seize civet cats in Xinyuan wildlife market in Guangzhou to prevent the spread of SARS-CoV. (Reproduced with permission from South China Morning Post). (b) The SARS-CoV expresses structural proteins — spike (S) protein, membrane (M), envelope (E) and nucleocapsid (N) and 14 open reading frames (ORFs). The spike protein determines the virus–host cell receptor interaction and is critical for host species restriction as well as being an important target for neutralizing antibody. (c) Transmission electron micrograph of FRhK cells infected with SARS-CoV. Viral particles are present on the surface of the cell with the particles showing the typical spikes or corona. (Courtesy of John Nicholls, Department of Pathology, The University of Hong Kong). (d) Organizing diffuse alveolar damage with giant cell formation in a patient who died of SARS. (Courtesy of John Nicholls, Department of Pathology, The University of Hong Kong).