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High-dimensional CyTOF analysis of dengue virus–infected human DCs reveals distinct viral signatures

Hamlin, RE, Rahman, A, Pak, TR, Maringer, Kevin, Mena, I, Bernal-Rubio, D, Potla, U, Maestre, AM, Fredericks, AC, Amir, El-ad D , Kasarskis, A, Ramos, I, Merad, M and Fernandez-Sesma, A (2017) High-dimensional CyTOF analysis of dengue virus–infected human DCs reveals distinct viral signatures JCI Insight, 2 (13), e92424.

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Abstract

Dengue virus (DENV) is the most prevalent mosquito-borne virus causing human disease. Of the 4 DENV serotypes, epidemiological data suggest that DENV-2 secondary infections are associated with more severe disease than DENV-4 infections. Mass cytometry by time-of-flight (CyTOF) was used to dissect immune changes induced by DENV-2 and DENV-4 in human DCs, the initial targets of primary infections that likely affect infection outcomes. Strikingly, DENV-4 replication peaked earlier and promoted stronger innate immune responses, with increased expression of DC activation and migration markers and increased cytokine production, compared with DENV-2. In addition, infected DCs produced higher levels of inflammatory cytokines compared with bystander DCs, which mainly produced IFN-induced cytokines. These high-dimensional analyses during DENV-2 and DENV-4 infections revealed distinct viral signatures marked by different replication strategies and antiviral innate immune induction in DCs, which may result in different viral fitness, transmission, and pathogenesis.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Hamlin, REUNSPECIFIEDUNSPECIFIED
Rahman, AUNSPECIFIEDUNSPECIFIED
Pak, TRUNSPECIFIEDUNSPECIFIED
Maringer, Kevink.maringer@surrey.ac.ukUNSPECIFIED
Mena, IUNSPECIFIEDUNSPECIFIED
Bernal-Rubio, DUNSPECIFIEDUNSPECIFIED
Potla, UUNSPECIFIEDUNSPECIFIED
Maestre, AMUNSPECIFIEDUNSPECIFIED
Fredericks, ACUNSPECIFIEDUNSPECIFIED
Amir, El-ad DUNSPECIFIEDUNSPECIFIED
Kasarskis, AUNSPECIFIEDUNSPECIFIED
Ramos, IUNSPECIFIEDUNSPECIFIED
Merad, MUNSPECIFIEDUNSPECIFIED
Fernandez-Sesma, AUNSPECIFIEDUNSPECIFIED
Date : 6 July 2017
Identification Number : 10.1172/jci.insight.92424
Copyright Disclaimer : Copyright © 2017 American Society for Clinical Investigation. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http:// creativecommons.org/licenses/by/4.0/.
Depositing User : Melanie Hughes
Date Deposited : 11 Jul 2017 08:45
Last Modified : 11 Jul 2017 08:58
URI: http://epubs.surrey.ac.uk/id/eprint/841590

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