SARS-Coronavirus Open Reading Frame-8b triggers intracellular stress pathways and activates NLRP3 inflammasomes

Shi, Chong-Shan; Nabar, Neel R.; Huang, Ning-Na; Kehrl, John H.

In 2002-2003 the SARS-CoV caused a severe respiratory illness affecting more than 8000 individuals with a mortality rate near 10% 1,2 . The subsequent identification of a large pool of coronaviruses circulating in bats and other animals portended the appearance of other highly pathogenic CoVs 3 , and in 2012 the Middle East Respiratory Syndrome-CoV caused a similar outbreak with a higher mortality rate 4 . Severe SARS-CoV infection manifests clinically as acute lung injury associated with high initial virus titers, macrophage/neutrophil accumulation in the lungs. and elevated proinflammatory serum cytokines (IL-1, IL-18, IL-6, IL-8, and MCP-1) [5] [6] [7] [8] . Recent advances have implicated inflammatory monocyte-macrophages (IMMs) in the lungs as critical mediators of SARS-CoV pathology, as a delayed type I interferon response promotes high initial virus titers and aberrant IMM recruitment 9 . Host disease is likely a combination of direct viral damage and consequences of an aberrant immune response promoted by IMMs 9 , underscoring the importance of determining the mechanisms by which the virus targets innate immunity.