脂滴促进肠道病毒复制Lipid Droplets Grease Enterovirus Replication

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Replication complexes of (+)RNA viruses of eukaryotes are associated with specialized membranous domains, termed replication organelles. How these structures develop is poorly understood. In a recent Cell paper, Laufman et al. (2019) reveal that enteroviruses recruit lipid droplets to support lipid synthesis required for the structural development of replication organelles.

Viral Generated Inter-Organelle Contacts Redirect Lipid Flux for Genome Replication


Highlights
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Poliovirus replication organelles form membrane contact sites with lipid droplets
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Contact sites enable transfer of essential lipids to the forming viral organelles
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Viral proteins mediate contact sites and interact with the host lipolysis machinery
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Inhibition of lipolysis or contact site formation disrupts enterovirus replication
Summary
Positive-stranded RNA viruses extensively remodel host cell architecture to enable viral replication. Here, we examined the poorly understood formation of specialized membrane compartments that are critical sites for the synthesis of the viral genome. We show that the replication compartments (RCs) of enteroviruses are created through novel membrane contact sites that recruit host lipid droplets (LDs) to the RCs. Viral proteins tether the RCs to the LDs and interact with the host lipolysis machinery to enable transfer of fatty acids from LDs, thereby providing lipids essential for RC biogenesis. Inhibiting the formation of the membrane contact sites between LDs and RCs or inhibition of the lipolysis pathway disrupts RC biogenesis and enterovirus replication. Our data illuminate mechanistic and functional aspects of organelle remodeling in viral infection and establish that pharmacological targeting of contact sites linking viral and host compartments is a potential strategy for antiviral development.
DOI:https://doi.org/10.1016/j.cell.2019.05.030