Dengue virus requires the CC-chemokine receptor CCR5 for replication and infection development

被引：54

作者：

Marques, Rafael E. ^{[1
]}

Guabiraba, Rodrigo ^{[2
]}

Del Sarto, Juliana L. ^{[1
]}

Rocha, Rebeca F. ^{[1
]}

Queiroz, Ana Luiza ^{[1
]}

Cisalpino, Daniel ^{[3
]}

Marques, Pedro E. ^{[4
]}

Pacca, Carolina C. ^{[5
]}

Fagundes, Caio T. ^{[3
]}

Menezes, Gustavo B. ^{[4
]}

Nogueira, Mauricio L. ^{[5
]}

Souza, Danielle G. ^{[3
]}

Teixeira, Mauro M. ^{[1
]}

机构：

[1] Univ Fed Minas Gerais, Inst Ciencias Biol, Immunopharmacol, Belo Horizonte, MG, Brazil

[2] INRA, UMR 1282, Infectiol & Sante Publ, F-37380 Nouzilly, France

[3] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, Microorganism Host Interact, Belo Horizonte, MG, Brazil

[4] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Morfol, Immunobiophoton, Belo Horizonte, MG, Brazil

[5] Fac Med Sao Jose do Rio Preto, Dept Doencas Dermatol Infecciosas & Parasitarias, Lab Pesquisa Virol, Sao Paulo, Brazil

来源：

IMMUNOLOGY | 2015年 / 145卷 / 04期

关键词：

CC-chemokine receptor 5; chemokines; dengue virus; inflammation; viral replication; WEST-NILE-VIRUS; IFN-GAMMA; PATHOGENESIS; RANTES; CELLS; ENDOCYTOSIS; EXPRESSION; RESISTANCE; DELETION; MODEL;

D O I：

10.1111/imm.12476

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Dengue is a mosquito-borne disease that affects millions of people worldwide yearly. Currently, there is no vaccine or specific treatment available. Further investigation on dengue pathogenesis is required to better understand the disease and to identify potential therapeutic targets. The chemokine system has been implicated in dengue pathogenesis, although the specific role of chemokines and their receptors remains elusive. Here we describe the role of the CC-chemokine receptor CCR5 in Dengue virus (DENV-2) infection. In vitro experiments showed that CCR5 is a host factor required for DENV-2 replication in human and mouse macrophages. DENV-2 infection induces the expression of CCR5 ligands. Incubation with an antagonist prevents CCR5 activation and reduces DENV-2 positive-stranded (+) RNA inside macrophages. Using an immunocompetent mouse model of DENV-2 infection we found that CCR5(-/-) mice were resistant to lethal infection, presenting at least 100-fold reduction of viral load in target organs and significant reduction in disease severity. This phenotype was reproduced in wild-type mice treated with CCR5-blocking compounds. Therefore, CCR5 is a host factor required for DENV-2 replication and disease development. Targeting CCR5 might represent a therapeutic strategy for dengue fever. These data bring new insights on the association between viral infections and the chemokine receptor CCR5.

引用

页码：583 / 596

页数：14

共 61 条

[1] Differential Requirements in Endocytic Trafficking for Penetration of Dengue Virus [J].

Acosta, Eliana G. ;

Castilla, Viviana ;

Damonte, Elsa B. .

PLOS ONE, 2012, 7 (09)

[2] CC CKRS: A RANTES, MIP-1 alpha, MIP-1 beta receptor as a fusion cofactor for macrophage-tropic HIV-1 [J].

Alkhatib, G ;

Combadiere, C ;

Broder, CC ;

Feng, Y ;

Kennedy, PE ;

Murphy, PM ;

Berger, EA .

SCIENCE, 1996, 272 (5270) :1955-1958

[3] Molecular mechanism of desensitization of the chemokine receptor CCR-5: receptor signaling and internalization are dissociable from its role as an HIV-1 co-receptor [J].

Aramori, I ;

Zhang, J ;

Ferguson, SSG ;

Bieniasz, PD ;

Cullen, BR ;

Caron, MG .

EMBO JOURNAL, 1997, 16 (15) :4606-4616

[4] Contribution of macrophage migration inhibitory factor to the pathogenesis of dengue virus infection [J].

Assuncao-Miranda, Iranaia ;

Amaral, Flavio A. ;

Bozza, Fernando A. ;

Fagundes, Caio T. ;

Sousa, Lirlandia P. ;

Souza, Danielle G. ;

Pacheco, Patricia ;

Barbosa-Lima, Giselle ;

Gomes, Rachel N. ;

Bozza, Patricia T. ;

Da Poian, Andrea T. ;

Teixeira, Mauro M. ;

Bozza, Marcelo T. .

FASEB JOURNAL, 2010, 24 (01) :218-228

[5]

Atrasheuskaya A, 2003, FEMS IMMUNOL MED MIC, V35, P33, DOI 10.1111/j.1574-695X.2003.tb00646.x

[6] Role of the chemokines CCL3/MIP-1α and CCL5/RANTES in sponge-induced inflammatory angiogenesis in mice [J].

Barcelos, Luciola S. ;

Coelho, Amanda M. ;

Russo, Remo C. ;

Guabiraba, Rodrigo ;

Souza, Adriano L. S. ;

Bruno-Lima, Guilherme, Jr. ;

Proudfoot, Amanda E. I. ;

Andrade, Silvia P. ;

Teixeira, Mauro M. .

MICROVASCULAR RESEARCH, 2009, 78 (02) :148-154

[7] The global distribution and burden of dengue [J].

Bhatt, Samir ;

Gething, Peter W. ;

Brady, Oliver J. ;

Messina, Jane P. ;

Farlow, Andrew W. ;

Moyes, Catherine L. ;

Drake, John M. ;

Brownstein, John S. ;

Hoen, Anne G. ;

Sankoh, Osman ;

Myers, Monica F. ;

George, Dylan B. ;

Jaenisch, Thomas ;

Wint, G. R. William ;

Simmons, Cameron P. ;

Scott, Thomas W. ;

Farrar, Jeremy J. ;

Hay, Simon I. .

NATURE, 2013, 496 (7446) :504-507

[8] Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity [J].

Bozza, Fernando A. ;

Cruz, Oswaldo G. ;

Zagne, Sonia Mo ;

Azeredo, Elzinandes L. ;

Nogueira, Rita M. R. ;

Assis, Edson F. ;

Bozza, Patricia T. ;

Kubelka, Claire F. .

BMC INFECTIOUS DISEASES, 2008, 8 (1)

[9] Primary acute dengue and the deletion in chemokine receptor 5 (CCR5Δ32) [J].

Brestovac, Brian ;

Halicki, Larissa A. ;

Harris, Ryan P. ;

Sampson, Ian ;

Speers, David J. ;

Mamotte, Cyril ;

Williams, David .

MICROBES AND INFECTION, 2014, 16 (06) :518-521

[10] The molecular biology of West Nile virus: A new invader of the Western hemisphere [J].

Brinton, MA .

ANNUAL REVIEW OF MICROBIOLOGY, 2002, 56 :371-402

← 1 2 3 4 5 6 7 →