Infection and activation of human peripheral blood monocytes by dengue viruses through the mechanism of antibody-dependent enhancement

Peifang Sun*, Karolis Bauza, Subhamoy Pal, Zhaodong Liang, Shuenn jue Wu, Charmagne Beckett, Timothy Burgess, Kevin Porter

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Human monocytes are susceptible to dengue virus (DV) infection through an FcR-dependent pathway known as antibody-dependent enhancement (ADE). In this study, infection enhancement was observed when purified monocytes were infected with DV serotypes in the presence of serially diluted immune serum antibodies. Analyzing binding of the DV-antibody immune complexes to monocytes by quantifying the amount of viruses attached to monocytes, we found that binding did not correlate with the input amount of antibodies; rather, it peaked at suboptimal antibody concentrations, correlating with the observed infection enhancement. These results suggested that immune complexes are involved in hindering DV from binding to FcR-bearing cells; when such a protective feature is weakened, enhancement of viral attachment and ADE are observed. Further, increased cytokine production (TNF-alpha and IFN-alpha), and costimulatory marker expression (CD86 and CD40), were found to be associated with infection enhancement, suggesting a pathological role of ADE-affected monocytes in dengue hemorrhagic diseases.

Original languageEnglish
Pages (from-to)245-252
Number of pages8
JournalVirology
Volume421
Issue number2
DOIs
StatePublished - 20 Dec 2011

Keywords

  • Antibody-dependent enhancement
  • Co-stimulatory markers
  • Cytokine
  • Dengue
  • Human monocytes

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