Fatty Acid Elongase 7 Catalyzes the Lipidome Remodeling Essential for Human Cytomegalovirus Replication
نویسندگان
چکیده
Human cytomegalovirus (HCMV) infection rewires host cell metabolism, up-regulating flux from glucose into acetyl-CoA to feed fatty acid metabolism, with saturated very long-chain fatty acids (VLFCA) required for production of infectious virion progeny. The human genome encodes seven elongase enzymes (ELOVL) that extend long chain fatty acids into VLCFA. Here we identify ELOVL7 as pivotal for HCMV infection. HCMV induces ELOVL7 by more than 150-fold. This induction is dependent on mTOR and SREBP-1. ELOVL7 knockdown or mTOR inhibition impairs HCMV-induced fatty acid elongation, HCMV particle release, and infectivity per particle. ELOVL7 overexpression enhances HCMV replication. During HCMV infection, mTOR activity is maintained by the viral protein pUL38. Expression of pUL38 is sufficient to induce ELOVL7, and pUL38-deficient virus is partially defective in ELOVL7 induction and fatty acid elongation. Thus, through its ability to modulate mTOR and SREBP-1, HCMV induces ELOVL7 to synthesize the saturated VLCFA required for efficient virus replication.
منابع مشابه
Fatty acid elongase 7 catalyzes lipidome remodeling essential for human cytomegalovirus replication.
Human cytomegalovirus (HCMV) infection rewires host-cell metabolism, upregulating flux from glucose into acetyl-CoA to feed fatty acid metabolism, with saturated very-long-chain fatty acids (VLFCAs) required for production of infectious virion progeny. The human genome encodes seven elongase enzymes (ELOVL) that extend long-chain fatty acids into VLCFA. Here, we identify ELOVL7 as pivotal for H...
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