Tomato bushy stunt virus builds unique membranous replication organelles that provide optimal lipid microenvironment.

Tombusviruses co-opt pre-existing subcellular membranes for replication.

Tombusviruses transport lipids into viral-replication organelles (VROs) in a nonvesicular pathway via co-opted lipid-transfer proteins.

Tombusviruses hijack lipid synthesis and lipid-modification enzymes into VROs.

Tombusviruses co-opt membrane-shaping and membrane-curvature-inducing proteins into VROs.

Positive-strand RNA viruses replicate in intracellular membranous structures formed after virus-driven intensive manipulation of subcellular organelles and membranes. These unique structures are called viral-replication organelles (VROs). To build VROs, the replication proteins coded by (+)RNA viruses co-opt host proteins, including membrane-shaping, lipid synthesis, and lipid-modification enzymes to create an optimal microenvironment that (i) concentrates the viral replicase and associated host proteins and the viral RNAs; (ii) regulates enzymatic activities and spatiotemporally the replication process; and (iii) protects the viral RNAs from recognition and degradation by the host innate immune defense. Tomato bushy stunt virus (TBSV), a plant (+)RNA virus, serves as an advanced model to study the interplay among viral components, co-opted host proteins, lipids, and membranes. This review presents our current understanding of the complex interaction between TBSV and host with panviral implications.

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