Molecular mechanisms of severe acute respiratory syndrome (SARS)

Abstract

Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network. The potential mutability of the SARS-CoV genome may lead to new SARS outbreaks and several regions of the viral genomes open reading frames have been identified which may contribute to the severe virulence of the virus. With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. Vaccination would offer the most attractive approach to prevent new epidemics of SARS, but the development of vaccines is difficult due to missing data on the role of immune system-virus interactions and the potential mutability of the virus. Even in a situation of no new infections, SARS remains a major health hazard, as new epidemics may arise. Therefore, further experimental and clinical research is required to control the disease.

Figure 1

Coronavirus classification. The family of coronaviruses belongs to the order of nidovirales and consists of three groups so far. It is still debatable whether the new SARS-CoV should be assigned to group II or to a new fourth group. Group I includes human coronavirus 229E (HCoV-229E), transmissible gastroenteritis virus (TEGV), porcine epidemic diarrhea virus (PEDV), canine coronavirus (CCoV), and feline coronavirus (FIPV). Group II viruses include human coronavirus OC43 (HCoV-OC43), murine hepatitis virus (MHV), and bovine coronavirus (BCoV), and group III species are turkey coronavirus (TCoV), and avian infectious bronchitis virus (IBV).

Figure 2

SARS-CoV genome organization. The structure of the SARS viral RNA is organized into 13–15 open reading frames (ORFs) and contains an overall amount of approximately 30,000 nucleotides. The sequence can be separated into different elements and genomic and subgenomic mRNAs.

Figure 3

SARS-CoV transmission electron microscopy. In the supernatant of SARS-CoV infected cytopathic Vero E6 cells, characteristic virus particles can be found. The diameter of the viruses ranges between 60 nm and 120 nm and the virus shapes are round or oval. There are many protrusions from the envelope which are arranged in order with wide gaps between them. There are also many virus particles in the infected cells present. They often form a virus vesicle with an encircling membrane. A: Higher magnification B: Lower magnification. Scale bars represent 100 nm. Reproduced with permission from Acta Biochimica et Biophysica Sinica 2003, 35(6):587–591 [126].

Figure 4

Potential target sites for therapeutic strategies. In view of the viral life cycle, there are several potential targets for the development of antiviral drugs. Starting from the binding of the virus to the target cell, the spike protein or receptors such as angiotension-converting enzyme 2 (ACE2), cell entry or the different replication steps may be targeted. After replication, virus assembly and exit mechanisms may also be used for antiviral strategies. VLP, virus-like particles.