PINLYP-mediated phospholipid metabolism reprogramming contributes to chronic herpesvirus infection

• DOI: 10.1371/journal.ppat.1013146
• Publication Date: 2025-05-15T17:32:51Z
• Authors: 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
• Keywords: Lytic cycle; Kaposi's sarcoma-associated herpesvirus

Many viruses alter the phospholipid metabolism to benefit their own life cycles. It is unclear whether host or virus driving reprogramming, and how infections are affected by metabolic status. Here we report that phospholipase A2 inhibitor LY6/PLAUR domain-containing protein (PINLYP) inhibits Kaposi’s sarcoma-associated herpesvirus (KSHV) lytic reactivation remodeling especially triacylglycerol (TAG) biosynthesis. PINLYP deficiency led increased cPLA2α activity, cPLA2α-mediated AKT phosphorylation, KSHV reactivation. Analyses of RNA-seq lipidomics reveal regulates long-chain fatty acid CoA ligase ACSL5 expression TAG production. The inhibition activity biosynthesis suppresses phosphorylation reactivation, restoring phenotype deficiency. This finding underscores pivotal role in promoting viral latency, which sheds new light on regulated provides a potential target for controlling chronic infection.