How mosquitoes turn viruses into human infection weapons
Scientists have identified why alphaviruses—including Chikungunya—become more dangerous when transmitted by mosquitoes rather than spreading between humans. The mosquito's unique lipid chemistry rewires the virus envelope to exploit a human immune receptor, suggesting new targets for vaccine and therapeutic development.
Originaltitel: TIM-1 promotes infection with mosquito cell-derived alphaviruses through virion-associated phospholipids
Human T-cell immunoglobulin and mucin domain 1 (TIM-1) facilitates infection of re-emerging viruses, including alphaviruses, through its phosphatidylserine (PS) binding domain. Although alphaviruses are transmitted to humans via mosquito bite, it is unclear whether mosquito-derived viruses also use TIM-1 to infect human cells. Since viruses acquire their PS-containing envelope from the host cell and insect cell membranes differ in lipid composition from mammalian membranes, we here investigate the role of TIM-1 at the mosquito-mammalian interface. We show that TIM-1 promotes infection with mosquito cell-derived, replication-competent alphaviruses, including Chikungunya virus, O'nyong'nyong virus (ONNV), and Sindbis virus. The TIM-1 PS-binding domain is essential for enhancing mosquito cell-derived ONNV infection as shown by TIM-1 mutagenesis. According to untargeted lipidomics, mosquito cell-derived ONNV virions contain higher levels of phosphatidylethanolamine (PE) and PS compared to mammalian cell-derived ONNV. Notably, TIM-1 engages PE as well as PS, as demonstrated by liposome competition. PS decarboxylase experiments suggest that PS is an important mediator of mosquito-cell derived ONNV entry into mammalian cells. Taken together, our data show that TIM-1 promotes mosquito cell-derived alphavirus infection of mammalian cells. This work provides implications for the understanding of the TIM-1 ligand repertoire and advances our understanding of arbovirus transmission at the mosquito-mammalian interface.