PMID- 36851679 OWN - NLM STAT- MEDLINE DCOM- 20230301 LR - 20230410 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 15 IP - 2 DP - 2023 Feb 7 TI - Global Lipidome Profiling Revealed Multifaceted Role of Lipid Species in Hepatitis C Virus Replication, Assembly, and Host Antiviral Response. LID - 10.3390/v15020464 [doi] LID - 464 AB - Hepatitis C virus (HCV) is a major human pathogen that requires a better understanding of its interaction with host cells. There is a close association of HCV life cycle with host lipid metabolism. Lipid droplets (LDs) have been found to be crucial organelles that support HCV replication and virion assembly. In addition to their role in replication, LDs also have protein-mediated antiviral properties that are activated during HCV infection. Studies have shown that HCV replicates well in cholesterol and sphingolipid-rich membranes, but the ways in which HCV alters host cell lipid dynamics are not yet known. In this study, we performed a kinetic study to check the enrichment of LDs at different time points of HCV infection. Based on the LD enrichment results, we selected early and later time points of HCV infection for global lipidomic study. Early infection represents the window period for HCV sensing and host immune response while later infection represents the establishment of viral RNA replication, virion assembly, and egress. We identified the dynamic profile of lipid species at early and later time points of HCV infection by global lipidomic study using mass spectrometry. At early HCV infection, phosphatidylinositol phospholipids (PIPs), lysophosphatidic acid (LPA), triacyl glycerols (TAG), phosphatidylcholine (PC), and trihexosylceramides (Hex3Cer) were observed to be enriched. Similarly, free fatty acids (FFA), phosphatidylethanolamine (PE), N-acylphosphatidylethanolamines (NAPE), and tri acylglycerols were enriched at later time points of HCV infection. Lipids enriched at early time of infection may have role in HCV sensing, viral attachment, and immune response as LPA and PIPs are important for immune response and viral attachment, respectively. Moreover, lipid species observed at later infection may contribute to HCV replication and virion assembly as PE, FFA, and triacylglycerols are known for the similar function. In conclusion, we identified lipid species that exhibited dynamic profile across early and later time points of HCV infection compared to mock cells, which could be therapeutically relevant in the design of more specific and effective anti-viral therapies. FAU - Islam, Khursheed Ul AU - Islam KU AD - Multidisciplinary Center for Advanced Research and Studies, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. FAU - Anwar, Saleem AU - Anwar S AD - Multidisciplinary Center for Advanced Research and Studies, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. FAU - Patel, Ayyub A AU - Patel AA AUID- ORCID: 0000-0002-5320-3202 AD - Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia. FAU - Mirdad, Mohammed Tarek AU - Mirdad MT AD - College of Medicine, King Khalid University, Abha 62529, Saudi Arabia. FAU - Mirdad, Mahmoud Tarek AU - Mirdad MT AD - College of Medicine, King Khalid University, Abha 62529, Saudi Arabia. FAU - Azmi, Md Iqbal AU - Azmi MI AD - Multidisciplinary Center for Advanced Research and Studies, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. FAU - Ahmad, Tanveer AU - Ahmad T AD - Multidisciplinary Center for Advanced Research and Studies, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. FAU - Fatima, Zeeshan AU - Fatima Z AD - Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, Bisha 61922, Saudi Arabia. AD - Amity Institute of Biotechnology, Amity University Haryana, Manesar, Gurugram 122413, India. FAU - Iqbal, Jawed AU - Iqbal J AD - Multidisciplinary Center for Advanced Research and Studies, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230207 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Antiviral Agents) RN - PDC6A3C0OX (Glycerol) SB - IM MH - Humans MH - *Hepacivirus MH - Lipidomics MH - *Hepatitis C MH - Antiviral Agents/pharmacology MH - Glycerol PMC - PMC9965260 OTO - NOTNLM OT - antiviral response OT - fatty acids OT - glycerolipids OT - glycerophospholipids OT - hepatitis C virus OT - lipidome COIS- Authors have declared no conflict of interest. EDAT- 2023/03/01 06:00 MHDA- 2023/03/03 06:00 PMCR- 2023/02/07 CRDT- 2023/02/28 01:41 PHST- 2022/12/20 00:00 [received] PHST- 2023/01/29 00:00 [revised] PHST- 2023/02/01 00:00 [accepted] PHST- 2023/02/28 01:41 [entrez] PHST- 2023/03/01 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2023/02/07 00:00 [pmc-release] AID - v15020464 [pii] AID - viruses-15-00464 [pii] AID - 10.3390/v15020464 [doi] PST - epublish SO - Viruses. 2023 Feb 7;15(2):464. doi: 10.3390/v15020464.