No one knew about the existence of inhibitory ligand of interferon receptors in the innate immune system. After over 13 years of hard work, Prof. Mingliang He’s team demonstrated that virus invasion upregulates and stimulates LRPAP1 secretion. As a ligand, the secreted LRPAP1 binds and triggers IFNAR1 degradation to facilitate virus evasion from cellular innate immunity. Targeting LRPAP1 with its inhibitor a2M potently inhibits infections by all the tested viruses (both DNA and RNA). This work not only expands the relationship between lipoprotein metabolism and the host's innate immune response but also paves the way for the development of LRPAP1 inhibitors as pan-antiviral drugs.
The research paper, titled “Secreted LRPAP1 binds and triggers IFNAR1 degradation to facilitate virus evasion from cellular innate immunity”, was published in the scientific journal Signal Transduction and Targeted Therapy. Please browse the article here (open access).