Enterovirus 71 Binding to PSGL-1 on Leukocytes: VP1-145 Acts as a Molecular Switch to Control Receptor Interaction. (PLoS pathogens, 2013, 9(7):e1003511)

報告日期: 2014/10/14
報告時間: 5:10/6:00
報告學生: 黃雅玲(以英文報告)
講評老師: 羅玉枝
附件下載: 下載[1431-1412164161-1.pdf] 

Enterovirus 71 Binding to PSGL-1 on Leukocytes: VP1- 145 Acts as a Molecular Switch to Control Receptor Interaction

Yorihiro Nishimura, Hyunwook Lee, Susan Hafenstein, Chikako Kataoka, Takaji Wakita, Jeffrey M. Bergelson, Hiroyuki Shimizu1

PLoS pathogens, 2013. 9(7):e1003511.

 

Speaker: Ya-Ling Huang (黃雅玲)              Time: 2014/10/14 17:10-18:00

Commentator:Prof. Yu-Chih Lo (羅玉枝老師) Place: Room 602

 

Abstract:

 

Enterovirus 71 has become endemic infectious diseases in Asia-Pacific region. Enterovirus 71 is a positive single-stranded RNA virus of the Picornaviridae family. PSGL-1 is recently identified well-known host receptor of enterovirus 71. According to PSGL-1-binding capacity, EV71 strains can be classified into two distinct phenotypes: PSGL-1-binding (PB) and PSGL-1-nonbinding (non-PB) strains. Firstly, the authors compared PB and non-PB strain sequences reveals four amino acid combinations at VP1-98 and VP1-145 within the VP1 region. 98.8% of the 1702 sequences found in GenBank database are clarified high frequent combinations. Subsequently, reverse genetics viruses interact with PSGL-1 indicate that VP-145 is the critical role for binding and for replicating in Jurkat cells. Furthermore, crystal structure reveal VP1-242K and VP1-244K surrounding VP1-145 could affect the orientation of lysine side chain exposed on the virus surface. After using co-immunoprecipitation PSGL-1 with VP1-K242A and/or VP1-K244A substitutions into two PB reverse genetics viruses, they measure enterovirus genome copies by real-time RT-PCR. Interestingly, mutation of VP1-244 abolished virus binding to PSGL-1, and mutation of VP1-242 reduced binding more than 100 fold. In conclusion, these results suggest that VP1-145 modulates the orientation of lysine VP1-244, and regulates exposure of the positively charged lysine side chain. The paper shed new light on virus-receptor interaction, and EV71

tropism for PSGL-1-expressing leukocytes.

 

Reference:

Nishimura, Yorihiro, et al. Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71. Nature medicine 15.7 (2009): 794-797.