The Emergence of Human Coronavirus EMC: How Scared Should We Be?

Chan, Renee W. Y.; Poon, Leo L. M.

The unusual severity of HCoV-EMC in humans, combined with its high fatality rate, is reminiscent of the clinical presentation of the SARS outbreak in 2003. SARS-CoV has strategies to limit host antiviral mechanisms by evading interferon (IFN) responses (8) . On the other hand, evidence from clinical and experimental studies suggests that SARS-CoV can induce cytokine dysregulation. Kindler et al. (5) delineate the immune response triggered by HCoV-EMC in HAE cultures by studying the proinflammatory gene expression profile upon HCoV-229E, HCoV-EMC, and SARS-CoV infection. The authors observed that both HCoV-229E and highly pathogenic coronaviruses can only marginally induce IFN and interferon-stimulating gene responses. In particular, HCoV-229E is found to be more capable of inducing proinflammatory gene expression, including tumor necrosis factor alpha (TNF-␣) and CXCL10, than the more pathogenic human coronaviruses. In contrast to the findings of Kindler et al., another previous study using well-differentiated normal human bronchial epithelial cells indicated that SARS-CoV induced higher cytokine and chemokine levels than HCoV-229E (9). This discrepancy may be attributed to different sampling times for cytokine and chemokine detection. In addition, one should note that SARS-CoV is known to modulate cytokine production by other key cells responsible for innate immunity in the lung (e.g., macrophage and dendritic cells) (10) . It is therefore essential to study HCoV-EMCinfected macrophages and dendritic cells. Furthermore, due to the nature of purified cell culture (e.g., HAE) models, cross talk between epithelial cells, macrophages, and dendritic cells cannot be evaluated. Additional experimental systems, such as ex vivo respiratory organ cultures and animal models, may provide further understanding of diseases caused by HCoV-EMC. In addition, clinical parameters determined from HCoV-EMC-infected patients would be extremely valuable for understanding the disease process in humans and could be used as a reference for data generated from in vitro and animal experiments.