A non-canonical JAK/STAT pathway promotes viral replication through the lipoprotein receptor-related protein in ticks

  • PLoS Biol. 2026 May 21;24(5):e3003797. doi: 10.1371/journal.pbio.3003797.
Yan Xu  1  2 ,  Wenbo Zeng  1  2 ,  Guodian Xiong  1  2 ,  Zhenhua Zheng  3 ,  Jingwen Wang  1  2
Affiliations
  • 1. State Key Laboratory of Genetics and Development of Complex Phenotypes, Department of Infectious Diseases, Fudan University, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 2. Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
  • 3. Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
PMID: 42166417 DOI: 10.1371/journal.pbio.3003797
Abstract

Ticks transmit numerous viruses that pose significant threats to human and animal health, however, the molecular interactions between ticks and viruses remain poorly understood. Using Langat virus (LGTV)-a surrogate for tick-borne encephalitis virus (TBEV), we show that the JAK/STAT pathway promotes viral Infection in Haemaphysalis longicornis. Rather than directly interacting with Viral Proteins, this proviral effect is mediated by a low-density lipoprotein receptor-related protein (LRP), whose expression is regulated by STAT. Silencing LRP in H. longicornis reduced LGTV Infection, while ectopic expression of LRP enhanced it. Unlike its mammalian counterparts, H. longicornis LRP lacks a transmembrane domain and localizes intracellularly. Functionally, LRP promotes lipophagy, leading to lipid droplets breakdown and providing energy to support viral replication. Together, these findings reveal a non-canonical mechanism by which the JAK/STAT pathway facilitates LGTV replication through STAT-dependent regulation of an atypical, intracellular LRP that drives lipophagy.

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