Lipids play numerous indispensable cellular functions and are involved in multiple steps in the replication cycle of viruses. Infections by human-pathogenic coronaviruses result in diverse clinical outcomes, ranging from self-limiting flu-like symptoms to severe pneumonia with extrapulmonary manifestations. Understanding how cellular lipids may modulate the pathogenicity of human-pathogenic coronaviruses remains poor. To this end, we utilized the human coronavirus 229E (HCoV-229E) as a model coronavirus to comprehensively characterize the host cell lipid response upon coronavirus infection with an ultra-high performance liquid chromatography-mass spectrometry (UPLC–MS)-based lipidomics approach. Our results revealed that glycerophospholipids and fatty acids (FAs) were significantly elevated in the HCoV-229E-infected cells and the linoleic acid (LA) to arachidonic acid (AA) metabolism axis was markedly perturbed upon HCoV-229E infection. Interestingly, exogenous supplement of LA or AA in HCoV-229E-infected cells significantly suppressed HCoV-229E virus replication. Importantly, the inhibitory effect of LA and AA on virus replication was also conserved for the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV). Taken together, our study demonstrated that host lipid metabolic remodeling was significantly associated with human-pathogenic coronavirus propagation. Our data further suggested that lipid metabolism regulation would be a common and druggable target for coronavirus infections.
【저자키워드】 MERS-CoV, HCoV-229E, Lipidomics, UHPLC–MS, 【초록키워드】 viruses, Coronavirus infection, coronavirus, Infection, metabolism, clinical outcomes, Replication, Coronavirus infections, understanding, Manifestations, virus replication, severe pneumonia, pathogenicity, function, Fatty acid, cellular, Lipid, lipid metabolism, Middle East, arachidonic acid, host cell, Regulation, inhibitory effect, respiratory syndrome coronavirus, human coronavirus 229E, highly pathogenic, Host, approach, Cell, conserved, significantly, involved, elevated, coronavirus, modulate, demonstrated, suggested, suppressed, flu-like symptom, 【제목키워드】 Human, Lipid, characterization, profile, remodeling,