Fatty acid elongase 7 catalyzes lipidome remodeling essential for human cytomegalovirus replication.

TitleFatty acid elongase 7 catalyzes lipidome remodeling essential for human cytomegalovirus replication.
Publication TypeJournal Article
Year of Publication2015
AuthorsPurdy, JG, Shenk, T, Rabinowitz, JD
JournalCell Rep
Volume10
Issue8
Pagination1375-85
Date Published2015 Mar 03
ISSN2211-1247
KeywordsAcetyltransferases, Biocatalysis, Cell Line, Cytomegalovirus, Fatty Acids, Humans, RNA Interference, RNA, Small Interfering, Sterol Regulatory Element Binding Protein 1, TOR Serine-Threonine Kinases, Viral Proteins, Virion, Virus Replication
Abstract

<p>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 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. </p>

DOI10.1016/j.celrep.2015.02.003
Alternate JournalCell Rep
PubMed ID25732827
PubMed Central IDPMC4354725
Grant ListGM71508 / GM / NIGMS NIH HHS / United States
AI78063 / AI / NIAID NIH HHS / United States
R01 CA082396 / CA / NCI NIH HHS / United States
P50 GM071508 / GM / NIGMS NIH HHS / United States
CA82396 / CA / NCI NIH HHS / United States
R01 AI097382 / AI / NIAID NIH HHS / United States
R01 AI078063 / AI / NIAID NIH HHS / United States