Proteomics

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Regulation of Global Lysine Lactylation during HCMV Infection

ABSTRACT: Aerobic glycolysis is a hallmark of virus-infected cells, leading to substantial accumulation and secretion of lactate. However, the regulatory roles of lactate during viral infections are still poorly understood. Here, we report that human cytomegalovirus (HCMV) infection leverages lactate to induce widespread protein lactylation and promote viral spread. Lactyllysine decorates intrinsically disordered regions (IDRs) of proteins, regulating viral protein condensates and immune signaling transduction. Dynamic lactylation of immune response pathways, a feature shared during infection with herpes simplex virus 1 (HSV-1), suppresses immunity through regulation of RBM14 and IFI16. K90 lactylation of the viral DNA sensor IFI16 blocks recruitment of the DNA-damage response master kinase DNA-PK, preventing IFI16-driven gene repression and cytokine responses. Together, we characterize global protein lactylation dynamics during virus infection, finding virus-induced lactate contributes to its immune evasion through direct inhibition of immune signaling pathways.

INSTRUMENT(S): timsTOF Ultra

ORGANISM(S): Cytomegalovirus Homo Sapiens (human)

TISSUE(S): Cell Culture, Fibroblast

SUBMITTER: Matthew Tyl  

LAB HEAD: Ileana Cristea

PROVIDER: PXD057709 | Pride | 2024-11-23

REPOSITORIES: pride

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Action DRS
20241031_LaIP_96hpi_0mM.d.zip Other
20241031_LaIP_96hpi_alanine.d.zip Other
20241031_LaIP_96hpi_shAARS1.d.zip Other
20241031_LaIP_96hpi_shScr.d.zip Other
20241031_WP_96hpi_0mM.d.zip Other
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Publications

Infection-induced lysine lactylation enables herpesvirus immune evasion.

Tyl Matthew D MD   Merengwa Victoria U VU   Cristea Ileana M IM  

Science advances 20250108 2

Aerobic glycolysis is a hallmark of many viral infections, leading to substantial accumulation of lactate. However, the regulatory roles of lactate during viral infections remain poorly understood. Here, we report that human cytomegalovirus (HCMV) infection leverages lactate to induce widespread protein lactylation and promote viral spread. We establish that lactyllysine is enriched in intrinsically disordered regions, regulating viral protein condensates and immune signaling transduction. Dynam  ...[more]

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