PINLYP-mediated phospholipid metabolism reprogramming contributes to chronic herpesvirus infection.
Many viruses alter the phospholipid metabolism to benefit their own life cycles. It is unclear whether the host or the virus is driving phospholipid metabolism reprogramming, and how virus infections are affected by the metabolic status. Here we report that phospholipase A2 inhibitor and LY6/PLAUR d...
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| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1013146 |
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| author | Zhangmengxue Lei Wendi Wei Mingyu Wang Yun Xu Lei Bai Ying Gao Congwei Jiang Fangxia Li Na Tian Linlin Kuang Ruiliang Zhu Gang Pang Ke Lan Suihan Feng Xiaozhen Liang |
| author_facet | Zhangmengxue Lei Wendi Wei Mingyu Wang Yun Xu Lei Bai Ying Gao Congwei Jiang Fangxia Li Na Tian Linlin Kuang Ruiliang Zhu Gang Pang Ke Lan Suihan Feng Xiaozhen Liang |
| author_sort | Zhangmengxue Lei |
| collection | DOAJ |
| description | Many viruses alter the phospholipid metabolism to benefit their own life cycles. It is unclear whether the host or the virus is driving phospholipid metabolism reprogramming, and how virus infections are affected by the metabolic status. Here we report that phospholipase A2 inhibitor and LY6/PLAUR domain-containing protein (PINLYP) inhibits Kaposi's sarcoma-associated herpesvirus (KSHV) lytic reactivation by remodeling phospholipid metabolism and especially triacylglycerol (TAG) biosynthesis. PINLYP deficiency led to increased phospholipase cPLA2α activity, cPLA2α-mediated AKT phosphorylation, and KSHV lytic reactivation. Analyses of RNA-seq and lipidomics reveal that PINLYP regulates long-chain fatty acid CoA ligase ACSL5 expression and TAG production. The inhibition of ACSL5 activity or TAG biosynthesis suppresses AKT phosphorylation and KSHV lytic reactivation, restoring the phenotype of PINLYP deficiency. This finding underscores the pivotal role of PINLYP in remodeling phospholipid metabolism and promoting viral latency, which sheds new light on how phospholipid metabolism is regulated by herpesvirus and provides a potential target for controlling chronic herpesvirus infection. |
| format | Article |
| id | doaj-art-ea47968009a34590a55c42ee5c16bb0b |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-ea47968009a34590a55c42ee5c16bb0b2025-08-20T03:13:39ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-05-01215e101314610.1371/journal.ppat.1013146PINLYP-mediated phospholipid metabolism reprogramming contributes to chronic herpesvirus infection.Zhangmengxue LeiWendi WeiMingyu WangYun XuLei BaiYing GaoCongwei JiangFangxia LiNa TianLinlin KuangRuiliang ZhuGang PangKe LanSuihan FengXiaozhen LiangMany viruses alter the phospholipid metabolism to benefit their own life cycles. It is unclear whether the host or the virus is driving phospholipid metabolism reprogramming, and how virus infections are affected by the metabolic status. Here we report that phospholipase A2 inhibitor and LY6/PLAUR domain-containing protein (PINLYP) inhibits Kaposi's sarcoma-associated herpesvirus (KSHV) lytic reactivation by remodeling phospholipid metabolism and especially triacylglycerol (TAG) biosynthesis. PINLYP deficiency led to increased phospholipase cPLA2α activity, cPLA2α-mediated AKT phosphorylation, and KSHV lytic reactivation. Analyses of RNA-seq and lipidomics reveal that PINLYP regulates long-chain fatty acid CoA ligase ACSL5 expression and TAG production. The inhibition of ACSL5 activity or TAG biosynthesis suppresses AKT phosphorylation and KSHV lytic reactivation, restoring the phenotype of PINLYP deficiency. This finding underscores the pivotal role of PINLYP in remodeling phospholipid metabolism and promoting viral latency, which sheds new light on how phospholipid metabolism is regulated by herpesvirus and provides a potential target for controlling chronic herpesvirus infection.https://doi.org/10.1371/journal.ppat.1013146 |
| spellingShingle | Zhangmengxue Lei Wendi Wei Mingyu Wang Yun Xu Lei Bai Ying Gao Congwei Jiang Fangxia Li Na Tian Linlin Kuang Ruiliang Zhu Gang Pang Ke Lan Suihan Feng Xiaozhen Liang PINLYP-mediated phospholipid metabolism reprogramming contributes to chronic herpesvirus infection. PLoS Pathogens |
| title | PINLYP-mediated phospholipid metabolism reprogramming contributes to chronic herpesvirus infection. |
| title_full | PINLYP-mediated phospholipid metabolism reprogramming contributes to chronic herpesvirus infection. |
| title_fullStr | PINLYP-mediated phospholipid metabolism reprogramming contributes to chronic herpesvirus infection. |
| title_full_unstemmed | PINLYP-mediated phospholipid metabolism reprogramming contributes to chronic herpesvirus infection. |
| title_short | PINLYP-mediated phospholipid metabolism reprogramming contributes to chronic herpesvirus infection. |
| title_sort | pinlyp mediated phospholipid metabolism reprogramming contributes to chronic herpesvirus infection |
| url | https://doi.org/10.1371/journal.ppat.1013146 |
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