The TIM and TAM Families of Phosphatidylserine Receptors Mediate Dengue Virus Entry

Cell Host & Microbe, Volume 12, Issue 4, 544-557, 18 October 2012

Speaker: Chao-Ho Li (李兆和)                                             Date: 15:00-16:00 Mar. 13, 2013

Commentator: Dr. Ching-Chuan Liu (劉清泉老師)             Place: Classroom 601

Abstract:

Dengue virus is an emerging virus which causes 50-100 million cases yearly. The most serious syndrome are DSS and DHS. The virus has four serotypes and no proper vaccine so far and the infectious area is widening due to global warming. Previous study has showed DV infects cell byclathrin-mediated endocytosis ^[1]and numerous receptors on cell surface such as DC-SIGN, L-SIGN and mannose receptors, which promote DV infection. But the molecular mechanism of how DV-host interactions for DV entry is still poorly understood. TIM and TAM are two transmembranereceptor families that participate in phosphatidylserine (PtdSer)-dependent phagocytosis^[2][3]. In this study, the author enhance DV infection rate by TIM cDNA transfection and proved that  TIM-enhanced DV entry is mediated by PtdSer on DV particles. By expressing TYRO3 and AXL, members of the TAM family, which are involved in apoptotic cell clearance on cell surface, DV infection rate is also enhanced. The authors discovered that the TIM and TAM did express on cell surfaces by screening the cell surface receptors of DV-infected cell lines. And the two receptors-facilitated DV entry phenomenon can be rescued by adding anti-TIM or anti-AXL mAb. In summary, these results indicated that inhibitor of TIM and TAM receptors may be a promising anti-viral drug.

References:

1.    Dissecting the Cell Entry Pathway of Dengue Virus by Single-Particle Tracking in Living Cells (distributed by Public Library of Science; released 2008), Article.

2.    Freeman, G.J., Casasnovas, J.M., Umetsu, D.T., & DeKruyff, R.H., TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity. Immunological Reviews 235 (1), 172-189 (2010).

3.    Lemke, G. & Rothlin, C.V., Immunobiology of the TAM receptors. Nat Rev Immunol 8 (5), 327-336 (2008).