Session topic

Title: The role of phosphatidylserine receptors TIM-1 and CD300a in Zika virus entry and infection: Potential as antiviral target?
ID: P 157
Type: ePoster self study
Session: ePoster self study
Receptors and entry

Speaker: Merel Oeyen (Leuven/BE), Dominique Schols (Leuven/BE)

Abstract - Text

Abstract text (incl. references and figure legends)

The Flavivirus Zika virus (ZIKV) still poses a major threat to public health because of several factors: in addition to transmission by virus-infected mosquitoes, it can also be vertically and sexually transmitted. Furthermore, it is associated with serious neurological complications such as fetal microcephaly and Guillain-Barré Syndrome. There is no vaccine or antiviral treatment available. To help contain predictedl future outbreaks, it is important that research focuses on strategies to target ZIKV transmission and infection. An attractive strategy is the inhibition of viral entry by targeting the interaction between ZIKV and cellular entry receptors. Phosphatidylserine receptors (PSR) are involved in Flavivirus entry by interacting with the envelope phospholipids, which allows endocytosis of the viral particle and further replication. A PSR of main interest is called the T cell Immunoglobulin and Mucin domain 1 (TIM-1). This receptor is known to bind and internalize dengue virus (DENV) particles, and is also suggested to be involved in ZIKV entry. Here, we further decipher the role of TIM-1 in ZIKV infection using TIM-1-transfected cells and by knocking down TIM-1 in cells endogenously expressing the receptor. We also investigate its role as antiviral target to inhibit ZIKV entry. To this end, we have optimized a flow cytometry-based functional phagocytosis assay to be able to study the role of TIM-1 inhibitors that also inhibit ZIKV infection. With this assay we can determine the effect of compounds on TIM-1 functioning. Finally, we also explore the usefulness of cellular electrical impedance measurements to screen potential TIM-1 ligands, to evaluate their anti-viral activity, cellular side-effects and toxicity, and to unravel underlying cellular pathways in real-time.

Another valuable and potential virus-involved PSR is called CD300a. It has been reported that this receptor is involved in dengue virus (DENV) attachment and entry. Using CD300a-transfected cells, we now demonstrate for the first time the role of CD300a in ZIKV entry and infection processes. We also show that ZIKV infection in CD300a-expressing macrophage-derived dendritic cells can be reduced by the addition of anti-CD300a antibodies.

To conclude, these results demonstrate that TIM-1 and CD300a deserve more attention are potential target receptors for antivirals to inhibit ZIKV and DENV entry and infection into susceptible host cells.