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PRRSV nucleocapsid and nonstructural proteins dual-regulate CD40 expression via ATF-2 and AP-1 pathways

Chaolun Fu1, Hongyan Gao1, Yingchao Li1

  • 1College of Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, China.

Veterinary Microbiology
|January 22, 2026
PubMed

Insights

Porcine reproductive and respiratory syndrome virus (PRRSV) alters macrophage CD40 expression. PRRSV nucleocapsid protein upregulates CD40, while other viral proteins downregulate it, offering potential antiviral targets.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Macrophage surface molecules are crucial for regulating inflammatory responses.
  • Porcine reproductive and respiratory syndrome virus (PRRSV) infects porcine alveolar macrophages, altering host surface receptor expression.
  • Understanding PRRSV's modulation of macrophage receptors is key to controlling infection.

Purpose of the Study:

  • To investigate the changes in immunoregulatory molecule expression on macrophages during PRRSV infection.
  • To identify specific PRRSV proteins involved in modulating CD40 expression.
  • To explore the functional consequence of CD40 modulation on PRRSV replication.

Main Methods:

  • Screening of immunoregulatory molecule expression in PRRSV-infected macrophages.
  • Reporter assays to assess the effect of viral proteins on CD40 promoter activity.
  • Analysis of transcription factor involvement (ATF-2, AP-1) in CD40 regulation.

Main Results:

  • CD40 was identified as the most significantly upregulated transcript in PRRSV-infected macrophages.
  • PRRSV nucleocapsid protein (N) enhanced CD40 promoter activity via ATF-2.
  • PRRSV nonstructural proteins Nsp1α, Nsp11, and Nsp12 suppressed CD40 promoter activity via AP-1.
  • Overexpression of CD40 restricted PRRSV replication.

Conclusions:

  • PRRSV differentially regulates CD40 expression through its nucleocapsid and nonstructural proteins.
  • CD40 plays a role in restricting PRRSV replication.
  • CD40 represents a potential therapeutic target for antiviral strategies against PRRSV.
Keywords:
AP-1ATF-2Anti-viral drugCD40Nonstructural proteinsNucleocapsid proteinPRRSV

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