Viral Load and Cytokine Response Profile Does Not Support Antibody-Dependent Enhancement in Dengue-Primed Zika Virus-Infected Patients

Clin Infect Dis. 2017 Oct 15;65(8):1260-1265. doi: 10.1093/cid/cix558.

Abstract

Background: The pathogenesis of severe dengue disease involves immune components as biomarkers. The mechanism by which some dengue virus (DENV)-infected individuals progress to severe disease is poorly understood. Most studies on the pathogenesis of severe dengue disease focus on the process of antibody-dependent enhancement (ADE) as a primary risk factor. With the circulation of Zika virus (ZIKV) in DENV-endemic areas, many people infected by ZIKV were likely exposed to DENV. The influence of such exposure on Zika disease outcomes remains unknown.

Methods: We investigated whether patients previously exposed to DENV exhibited higher viremia when exposed to a subsequent, heterologous dengue or Zika infection than those patients not previously exposed to dengue. We measured viral loads and cytokine profile during patients' acute infections.

Results: Neither dengue nor Zika viremia was higher in patients with prior DENV infection, although the power to detect such a difference was only adequate in the ZIKV analysis. Of the 10 cytokines measured, only 1 significant difference was detected: Levels of interleukin 1β (IL-1β) were lower in dengue-infected patients who had experienced a previous dengue infection than patients infected with dengue for the first time. However, power to detect differences between groups was low. In Zika-infected patients, levels of IL-1β showed a significant, positive correlation with viral load.

Conclusions: No signs of ADE were observed in vivo in patients with acute ZIKV infection who had prior exposure to DENV.

Keywords: ADE; DENV; ZIKV; cytokines.

MeSH terms

  • Adolescent
  • Adult
  • Antibody-Dependent Enhancement / immunology*
  • Child
  • Cohort Studies
  • Cytokines / blood*
  • Dengue / epidemiology
  • Dengue / immunology*
  • Humans
  • RNA, Viral / blood
  • Viral Load / statistics & numerical data
  • Viremia
  • Young Adult
  • Zika Virus / immunology*
  • Zika Virus Infection / blood
  • Zika Virus Infection / epidemiology
  • Zika Virus Infection / immunology*
  • Zika Virus Infection / virology*

Substances

  • Cytokines
  • RNA, Viral