image: Model of the role of claudin-11 in the CME of influenza virus
Credit: ©Science China Press
This study is reported by Hualan Chen’s group from the State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences. Entry of influenza virus into the host cell is a key process in viral infection, which includes two steps: binding and internalization. Most influenza virus particles are internalized cells via clathrin-mediated endocytosis (CME) using metabotropic glutamate receptor subtype 2 (mGluR2) as an endocytic receptor. A previous study indicates that potassium calcium-activated channel subfamily M alpha 1 (KCa1.1) interacts with mGluR2 to initiate influenza virus CME, and activated KCa1.1 causes the polymerization of F-actin, which is required for the formation of clathrin-coated pits (CCPs). However, unlike the endocytic receptor mGluR2, KCa1.1 is not internalized with the influenza virus, suggesting that other host factor(s) may be involved in this process and disrupt the interaction between KCa1.1 and mGluR2.
In this study, the researchers find that claudin-11, a four-transmembrane protein encoded by claudin-11, plays an integral part in influenza virus CME. Claudin-11 interacts directly with mGluR2 to lead to the dissociation of KCa1.1 from mGluR2. Subsequently, claudin-11, together with mGluR2, is internalized into influenza virus-containing CCPs. Within these CCPs, claudin-11 facilitates the depolymerization of the polymerized F-actin, ultimately promoting the maturation of the influenza virus-containing clathrin-coated vehicles. Importantly, more than 60% of claudin-11-silenced mice survived infection with a lethal influenza virus, highlighting the potential of targeting claudin-11 for antiviral drug development.
In summary, this study identified a key host factor that promotes influenza virus infection and elucidated its underlying mechanism. This finding not only advances the understanding of influenza virus infection, but also opens a new window for host-based antiviral drug development.
See the article:
Claudin-11 plays a pivotal role in the clathrin-mediated endocytosis of influenza A virus
Journal
Science China Life Sciences