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<p>Herpes simplex virus type 1 (HSV-1) triggers significant inflammation and immune dysregulation, particularly in immunocompromised hosts. MicroRNA-221 (miR-221) is implicated in viral pathogenesis and inflammatory responses, yet its role in HSV-1 infection remains undefined. This study demonstrates that miR-221 suppresses HSV-1 replication, with 100 nM miR-221 reducing plaque formation by approximately 70% and markedly decreasing infectious viral titers (TCID<sub>50</sub>) <i>in vitro.</i> Mechanistically, bioinformatic analyses, dual-luciferase reporting, and RNA immunoprecipitation (RIP) confirmed CAMK2A, a calcium-signaling kinase, as a direct target of miR-221. KEGG pathway mapping linked miR-221 to calcium signaling, complement activation, and extracellular matrix interactions. In vivo, miR-221 overexpression in HSV-1–infected mouse corneas reduced pro-inflammatory cytokines (TNF-α, IL-6) and elevated anti-inflammatory IL-10, while enhancing CD8<sup>+</sup> T-cell and NK-cell activation. Critically, it attenuated inflammatory cell infiltration and tissue apoptosis. CAMK2A inhibition synergistically amplified these antiviral and anti-inflammatory effects, whereas CAMK2A overexpression reversed them. We conclude that miR-221 restricts HSV-1 replication and modulates host inflammation by recruiting RISC to silence CAMK2A, thereby disrupting calcium signaling and promoting immune activation. These findings identify the miR-221/CAMK2A axis as a promising therapeutic target for HSV-1-induced inflammation.</p>

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miR-221 Exerts Antiviral and Anti-Inflammatory Effects against HSV-1 Through Direct Repression of CAMK2A and Immune Pathway Activation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月19日

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  • Jiahao Xu,
  • Lianhong Xu,
  • Die Hu,
  • Ying Zhang,
  • Yongfang Wang,
  • Zhihua Yun

摘要

Herpes simplex virus type 1 (HSV-1) triggers significant inflammation and immune dysregulation, particularly in immunocompromised hosts. MicroRNA-221 (miR-221) is implicated in viral pathogenesis and inflammatory responses, yet its role in HSV-1 infection remains undefined. This study demonstrates that miR-221 suppresses HSV-1 replication, with 100 nM miR-221 reducing plaque formation by approximately 70% and markedly decreasing infectious viral titers (TCID50) in vitro. Mechanistically, bioinformatic analyses, dual-luciferase reporting, and RNA immunoprecipitation (RIP) confirmed CAMK2A, a calcium-signaling kinase, as a direct target of miR-221. KEGG pathway mapping linked miR-221 to calcium signaling, complement activation, and extracellular matrix interactions. In vivo, miR-221 overexpression in HSV-1–infected mouse corneas reduced pro-inflammatory cytokines (TNF-α, IL-6) and elevated anti-inflammatory IL-10, while enhancing CD8+ T-cell and NK-cell activation. Critically, it attenuated inflammatory cell infiltration and tissue apoptosis. CAMK2A inhibition synergistically amplified these antiviral and anti-inflammatory effects, whereas CAMK2A overexpression reversed them. We conclude that miR-221 restricts HSV-1 replication and modulates host inflammation by recruiting RISC to silence CAMK2A, thereby disrupting calcium signaling and promoting immune activation. These findings identify the miR-221/CAMK2A axis as a promising therapeutic target for HSV-1-induced inflammation.