High-dimensional CyTOF analysis of dengue virus–infected human DCs reveals distinct viral signatures
2017
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.
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