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Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
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Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
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The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
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Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
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Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
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CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats is a adaptive immune system found in bacteria and archaea that protects against viral infections. This system enables prokaryotic cells to identify, remember, and neutralize foreign genetic elements, primarily bacteriophages, by storing fragments of the invader’s DNA as a genetic memory.The CRISPR immune response begins during an initial infection. Cas (CRISPR-associated) proteins play a central role in this...
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Palmitic Acid Promotes Antiviral Innate Immunity via ZDHHC20-Mediated CMPK2 Palmitoylation.

Yujia Wang1,2, Zenghui Cui2, Yunkai Zhang3

  • 1Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|April 21, 2026
PubMed
Summary

Palmitic acid activates antiviral immunity by modifying UMP-CMP kinase 2 (CMPK2). Targeting the PPT1 enzyme enhances this response, offering potential treatments for RNA virus infections.

Keywords:
CMPK2IFN‐Iimmunometabolisminnate immune responsepalmitoylation

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Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE
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Area of Science:

  • Immunology
  • Virology
  • Metabolism

Background:

  • Immunometabolic crosstalk is vital for antiviral defense but poorly understood.
  • Regulation via post-translational modifications, especially in macrophages, needs clarification.

Purpose of the Study:

  • To identify metabolites that activate antiviral immunity.
  • To elucidate the role of palmitic acid (PA) and its downstream effects on antiviral pathways.

Main Methods:

  • Screening a metabolic chemical library to identify immune activators.
  • Investigating the palmitoylation of UMP-CMP kinase 2 (CMPK2) and its impact on mitochondrial antiviral signaling protein (MAVS).
  • Analyzing the roles of ZDHHC20 and PPT1 in CMPK2 modification and antiviral response.

Main Results:

  • Palmitic acid (PA) was identified as an activator of antiviral immunity in macrophages.
  • PA induces CMPK2 palmitoylation, crucial for mitochondrial localization, ddhCTP production, and MAVS stabilization.
  • CMPK2 deficiency impairs IFN-I production and increases viral replication; PPT1 deficiency restores antiviral immunity.

Conclusions:

  • The PA-ZDHHC20-CMPK2-PPT1 axis enhances antiviral responses.
  • Targeting PPT1, for instance with inhibitor DC661 or via dietary interventions, boosts IFN-I production and holds potential for treating RNA virus infections.