{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:43:23Z","timestamp":1790700203672,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T00:00:00Z","timestamp":1684108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council (NHMRC) of Australia","doi-asserted-by":"publisher","award":["1003767"],"award-info":[{"award-number":["1003767"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council (NHMRC) of Australia","doi-asserted-by":"publisher","award":["1047417"],"award-info":[{"award-number":["1047417"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council (NHMRC) of Australia","doi-asserted-by":"publisher","award":["1053206"],"award-info":[{"award-number":["1053206"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Sydney","award":["1003767"],"award-info":[{"award-number":["1003767"]}]},{"name":"University of Sydney","award":["1047417"],"award-info":[{"award-number":["1047417"]}]},{"name":"University of Sydney","award":["1053206"],"award-info":[{"award-number":["1053206"]}]},{"name":"Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney","award":["1003767"],"award-info":[{"award-number":["1003767"]}]},{"name":"Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney","award":["1047417"],"award-info":[{"award-number":["1047417"]}]},{"name":"Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney","award":["1053206"],"award-info":[{"award-number":["1053206"]}]},{"name":"PhD Overseas Scholarship from the Ministry of Health, Kingdom of Saudi Arabia","award":["1003767"],"award-info":[{"award-number":["1003767"]}]},{"name":"PhD Overseas Scholarship from the Ministry of Health, Kingdom of Saudi Arabia","award":["1047417"],"award-info":[{"award-number":["1047417"]}]},{"name":"PhD Overseas Scholarship from the Ministry of Health, Kingdom of Saudi Arabia","award":["1053206"],"award-info":[{"award-number":["1053206"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The hepatitis C virus (HCV) relies on cellular lipid pathways for virus replication and also induces liver steatosis, but the mechanisms involved are not clear. We performed a quantitative lipidomics analysis of virus-infected cells by combining high-performance thin-layer chromatography (HPTLC) and mass spectrometry, using an established HCV cell culture model and subcellular fractionation. Neutral lipid and phospholipids were increased in the HCV-infected cells; in the endoplasmic reticulum there was an ~four-fold increase in free cholesterol and an ~three-fold increase in phosphatidyl choline (p &lt; 0.05). The increase in phosphatidyl choline was due to the induction of a non-canonical synthesis pathway involving phosphatidyl ethanolamine transferase (PEMT). An HCV infection induced expression of PEMT while knocking down PEMT with siRNA inhibited virus replication. As well as supporting virus replication, PEMT mediates steatosis. Consistently, HCV induced the expression of the pro-lipogenic genes SREBP 1c and DGAT1 while inhibiting the expression of MTP, promoting lipid accumulation. Knocking down PEMT reversed these changes and reduced the lipid content in virus-infected cells. Interestingly, PEMT expression was over 50% higher in liver biopsies from people infected with the HCV genotype 3 than 1, and three times higher than in people with chronic hepatitis B, suggesting that this may account for genotype-dependent differences in the prevalence of hepatic steatosis. PEMT is a key enzyme for promoting the accumulation of lipids in HCV-infected cells and supports virus replication. The induction of PEMT may account for virus genotype specific differences in hepatic steatosis.<\/jats:p>","DOI":"10.3390\/ijms24108781","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T02:37:51Z","timestamp":1684204671000},"page":"8781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["PEMT Mediates Hepatitis C Virus-Induced Steatosis, Explains Genotype-Specific Phenotypes and Supports Virus Replication"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9663-8874","authenticated-orcid":false,"given":"Mosleh","family":"Abomughaid","sequence":"first","affiliation":[{"name":"Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enoch S. E.","family":"Tay","sequence":"additional","affiliation":[{"name":"Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Pickford","sequence":"additional","affiliation":[{"name":"Bioanalytical Mass Spectrometry Facility, Mark Wainright Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandra","family":"Malladi","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, School of Medicine, Western Sydney University, Sydney, NSW 2751, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6775-2061","authenticated-orcid":false,"given":"Scott A.","family":"Read","sequence":"additional","affiliation":[{"name":"Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, NSW 2145, Australia"},{"name":"Blacktown Clinical School, Western Sydney University and Blacktown Hospital, Sydney, NSW 2751, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8048-7370","authenticated-orcid":false,"given":"Jens R.","family":"Coorssen","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology, School of Medicine, Western Sydney University, Sydney, NSW 2751, Australia"},{"name":"Department of Biological Sciences, Faculty of Mathematics and Science, Brock University, St. Catharines, ON L2S 3A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian S.","family":"Gloss","sequence":"additional","affiliation":[{"name":"Westmead Research Hub, Westmead Institute for Medical Research, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8421-5476","authenticated-orcid":false,"given":"Jacob","family":"George","sequence":"additional","affiliation":[{"name":"Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4621-3485","authenticated-orcid":false,"given":"Mark W.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Storr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney and Westmead Hospital, Sydney, NSW 2145, Australia"},{"name":"Centre for Infectious Diseases and Microbiology, Sydney Infectious Diseases Institute, The University of Sydney at Westmead Hospital, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bley, H., Sch\u00f6bel, A., and Herker, E. 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