Interaction between hTIM-1 and Envelope Protein Is Important for JEV Infection

Abstract

Japanese encephalitis virus (JEV), a mosquito-borne zoonotic virus, is one of the most important causes of human viral encephalitis. JEV relies on various attachment or entry co-factors to enter host cells. Among these co-factors, hTIM-1 has been identified as an attachment factor to promote JEV infection through interacting with phosphatidylserine (PS) on the viral envelope. However, the reasons why JEV prefers to use hTIM-1 over other PS binding receptors are unknown. Here, we demonstrated that hTIM-1 can directly interact with JEV E protein. The interaction between hTIM-1 and JEV relies on specific binding sites, respectively, ND114115 in the hTIM-1 IgV domain and K38 of the E protein. Furthermore, during the early stage of infection, hTIM-1 and JEV are co-internalized into cells and transported into early and late endosomes. Additionally, we found that the hTIM-1 soluble ectodomain protein effectively inhibits JEV infection in vitro. Moreover, hTIM-1-specific antibodies have been shown to downregulate JEV infectivity in cells. Taken together, these findings suggested that hTIM-1 protein directly interacts with JEV E protein and mediates JEV infection, in addition to the PS-TIM-1 interaction.

Current Advances in Japanese Encephalitis Virus Drug Development

“…The identification of host and viral factors involved in JEV entry has been an active area of scientific investigation in the literature. Many different molecules have been demonstrated to interact with JEV on the cell surface, and several studies have identified potential receptors such as heat shock protein, glucose-regulated protein 78 (GRP78), C-type lectin member 5A (CLEC5A), T-cell immunoglobulin and mucin domain 1 (TIM-1), dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), vimentin, laminin receptor, and CD4 in different cell types [ 10 , 19 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ].…”

Advances in Alphavirus and Flavivirus Research

“…Liang et al show that hTIM-1 protein can directly interact with Japanese encephalitis virus (JEV) E protein and mediates JEV infection and that this interaction was found to be on specific binding sites between ND114115 in the hTIM-1 IgV domain and K38 of the E protein [ 20 ].…”