Fig 9. Schematic model of TREM2 regulation of PRRSV infection.

TREM2 downregulation promotes the recruitment of Syk and the activation of downstream PI3K/Akt and ERK1/2 pathways. Simultaneously, TLR4-NF-κB signaling is triggered early in the viral infection, leading to an intensive and sustained proinflammatory response. Elevated proinflammatory cytokines and type I interferons reduce the expression of CD163 and increase the cleavage of CD163 mediated by ADAM17, which contributes to suppression of PRRSV infection. On the contrary, the cytoplasmic tail of TREM2 interacted with PRRSV Nsp2 to promote infection. Meanwhile, exogenous sTREM2 blocks PRRSV binding to cell receptors via competitively interacting with viral envelope proteins.