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Researchers discovered that the JAK/STAT signaling pathway in ticks promotes viral replication through an unexpected mechanism involving a modified lipoprotein receptor-related protein (LRP). Unlike mammalian versions, the tick LRP lacks a transmembrane domain and functions inside cells to trigger lipophagy—the breakdown of lipid droplets—which provides energy for viral replication. This study used Langat virus as a model for tick-borne encephalitis virus in Haemaphysalis longicornis ticks.
Why it matters
Understanding how ticks support viral replication at the molecular level could lead to new strategies for controlling tick-borne diseases that threaten human and animal health. The discovery of this non-canonical pathway presents potential targets for interventions that could disrupt virus transmission by ticks.
by Yan Xu, Wenbo Zeng, Guodian Xiong, Zhenhua Zheng, Jingwen Wang
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.