Human coronavirus (HCoV) infection causes respiratory diseases with mild to 
severe outcomes. In the last 15 years, we have witnessed the emergence of two 
zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus 
(SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). 
Replication of HCoV is regulated by a diversity of host factors and induces 
drastic alterations in cellular structure and physiology. Activation of critical 
signaling pathways during HCoV infection modulates the induction of antiviral 
immune response and contributes to the pathogenesis of HCoV. Recent studies have 
begun to reveal some fundamental aspects of the intricate HCoV-host interaction 
in mechanistic detail. In this review, we summarize the current knowledge of 
host factors co-opted and signaling pathways activated during HCoV infection, 
with an emphasis on HCoV-infection-induced stress response, autophagy, 
apoptosis, and innate immunity. The cross talk among these pathways, as well as 
the modulatory strategies utilized by HCoV, is also discussed.