In:
Immunology, Wiley, Vol. 145, No. 4 ( 2015-08), p. 583-596
Abstract:
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 CCR 5 in Dengue virus ( DENV ‐2) infection. In vitro experiments showed that CCR 5 is a host factor required for DENV ‐2 replication in human and mouse macrophages. DENV ‐2 infection induces the expression of CCR 5 ligands. Incubation with an antagonist prevents CCR 5 activation and reduces DENV ‐2 positive‐stranded (+) RNA inside macrophages. Using an immunocompetent mouse model of DENV ‐2 infection we found that CCR 5 −/− 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 CCR 5‐blocking compounds. Therefore, CCR 5 is a host factor required for DENV ‐2 replication and disease development. Targeting CCR 5 might represent a therapeutic strategy for dengue fever. These data bring new insights on the association between viral infections and the chemokine receptor CCR 5.
Type of Medium:
Online Resource
ISSN:
0019-2805
,
1365-2567
DOI:
10.1111/imm.2015.145.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2006481-0
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