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The inflammasome-activating poxvirus peptide IAMP29 promotes antimicrobial and anticancer responses

Taylor Roh1,2,3,4, Wonhyoung Seo1,2, Minho Won5

  • 1Department of Microbiology, Chungnam National University College of Medicine, Daejeon, Republic of Korea.

Experimental & Molecular Medicine
|November 7, 2024
PubMed

Insights

Monkeypox virus envelope peptide IAMP29 activates the NLRP3 inflammasome, boosting innate immunity and showing potential for treating infections and leukemia.

Area of Science:

  • Virology and Immunology
  • Infectious Disease Mechanisms
  • Innate Immune Response Modulation

Background:

  • Poxviruses cause diverse infections, but underlying immune response mechanisms remain poorly understood.
  • The monkeypox virus envelope protein (A30L) and its derived peptide (IAMP29) were investigated for their role in innate immunity.

Purpose of the Study:

  • To elucidate the function and mechanisms of monkeypox virus A30L protein and IAMP29 in activating innate immune responses.
  • To explore the therapeutic potential of IAMP29 in infectious diseases and cancer.

Main Methods:

  • Investigated inflammasome activation by A30L and IAMP29 in human monocytes and murine macrophages.
  • Assessed mitochondrial reactive oxygen species production, metabolic reprogramming (glycolysis), and pyruvate kinase M interactions.
  • Evaluated IAMP29's effect on antimicrobial responses against non-tuberculous mycobacteria and its cytotoxic activity against leukemia cells.

Main Results:

  • A30L and IAMP29 potently activated the NLRP3 inflammasome, inducing interleukin-1β production via mitochondrial reactive oxygen species.
  • IAMP29 triggered glycolysis and interacted with PKM1/PKM2, leading to inflammasome activation in monocytes and macrophages.
  • IAMP29 enhanced antimicrobial responses and exhibited pyroptosis and apoptosis-mediated cytotoxicity against leukemia cells.

Conclusions:

  • Monkeypox virus envelope peptide IAMP29 is a potent activator of the NLRP3 inflammasome, driving innate immune responses.
  • IAMP29 demonstrates therapeutic potential for infectious diseases and leukemia through inflammasome activation and direct cytotoxicity.

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