Reciprocal Effects of Fibroblast Growth Factor Receptor Signaling on Dengue Virus Replication and Virion Production

被引：17

作者：

Cortese, Mirko ^{[1
]}

Kumar, Anil ^{[1
,11
]}

Matula, Petr ^{[2
,3
,8
]}

Kaderali, Lars ^{[4
,9
]}

Scaturro, Pietro ^{[1
,10
]}

Erfle, Holger ^{[5
]}

Acosta, Eliana Gisela ^{[1
]}

Buehler, Sandra ^{[1
]}

Ruggieri, Alessia ^{[1
]}

Chatel-Chaix, Laurent ^{[1
,7
]}

Rohr, Karl ^{[2
,3
]}

Bartenschlager, Ralf ^{[1
,6
]}

机构：

[1] Heidelberg Univ, Dept Infect Dis, Mol Virol, Neuenheimer Feld 344, D-69120 Heidelberg, Germany

[2] Heidelberg Univ, Biomed Comp Vis Grp, BioQuant, IPMB, Neuenheimer Feld 267, D-69120 Heidelberg, Germany

[3] German Canc Res Ctr, Neuenheimer Feld 267, D-69120 Heidelberg, Germany

[4] Heidelberg Univ, ViroQuant Res Grp Modeling, BioQuant, Heidelberg, Germany

[5] Heidelberg Univ, Adv Biol Screening Facil, BioQuant, D-69120 Heidelberg, Germany

[6] German Ctr Infect Res, Heidelberg Partner Site,Neuenheimer Feld 344, D-69120 Heidelberg, Germany

[7] Inst Armand Frappier, Inst Natl Rech Sci, 531 Blvd Prairies Laval, Quebec City, PQ H7V 1B7, Canada

[8] Masaryk Univ, Fac Informat, Bot 68a, Brno 60200, Czech Republic

[9] Univ Med Greifswald, Inst Bioinformat, Walther Rathenau Str 48, D-17475 Greifswald, Germany

[10] Tech Univ Munich, Inst Virol, Sch Med, Schneckenburgerstr 8, D-81675 Munich, Germany

[11] Univ Alberta, Dept Cell Biol, Edmonton, AB, Canada

来源：

CELL REPORTS | 2019年 / 27卷 / 09期

关键词：

HOST FACTORS; ZIKA VIRUS; ACTIVATION; PATHWAY; KINASE; IDENTIFICATION; RESIDUES; MUTATION;

D O I：

10.1016/j.celrep.2019.04.105

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Dengue virus (DENV) is a human arboviral pathogen accounting for 390 million infections every year. The available vaccine has limited efficacy, and DENV-specific drugs have not been generated. To better understand DENV-host cell interaction, we employed RNA interference-based screening of the human kinome and identified fibroblast growth factor receptor 4 (FGFR4) to control the DENV replication cycle. Pharmacological inhibition of FGFR exerts a reciprocal effect by reducing DENV RNA replication and promoting the production of infectious virus particles. Addressing the latter effect, we found that the FGFR signaling pathway modulates intracellular distribution of DENV particles in a PI3K-dependent manner. Upon FGFR inhibition, virions accumulate in the trans-Golgi network compartment, where they undergo enhanced maturation cleavage of the envelope protein precursor membrane (prM), rendering virus particles more infectious. This study reveals an unexpected reciprocal role of a cellular receptor tyrosine kinase regulating DENV RNA replication and the production of infectious virions.

引用

页码：2579 / +

页数：20

共 53 条

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