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

• Published in: Clinical infectious diseases Vol. 65; no. 8; pp. 1260 - 1265
• Main Authors: Terzian, Ana Carolina Bernardes, Schanoski, Alessandra Soares, de Oliveira Mota, Mânlio Tasso, da Silva, Rafael Alves, Estofolete, Cássia Fernanda, Colombo, Tatiana Elias, Rahal, Paula, Hanley, Kathryn A., Vasilakis, Nikos, Kalil, Jorge, Nogueira, Maurício Lacerda
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15.10.2017
• Subjects: and Commentaries; ARTICLES AND COMMENTARIES; Biomarkers; Cytokines; Dengue fever; Dengue hemorrhagic fever; Exposure; IL-1β; Infections; Interleukins; Pathogenesis; Patients; Risk factors; Vector-borne diseases; Viral diseases; Viremia; Viruses; Zika virus; ZIKV; ADE; cytokines; DENV
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/cix558

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.