Multifaceted Roles of TIM-Family Proteins in Virus-Host Interactions

To enhance infection, enveloped viruses exploit adhesion molecules expressed on the surface of host cells. Specifically, phosphatidylserine (PS) receptors - including members of the human T cell immunoglobulin and mucin domain (TIM)-family - have gained attention for their ability to mediate the entry of many enveloped viruses. However, recent evidence that TIM-1 can restrict viral release reveals a new role for these PS receptors. Additionally, viral factors such as the HIV-1 accessory protein Nef can antagonize this antiviral activity of TIM-1 while host restriction factors such as SERINC5 can enhance it. In this review, we examine the various roles of PS receptors, specifically TIM-family proteins, and the intricate relationship between host and viral factors. Elucidating the multifunctional roles of PS receptors in virus-host interaction is important for understanding viral pathogenesis and developing novel antiviral therapeutics.