Primary dengue haemorrhagic fever in patients from northeast of Brazil is associated with high levels of interferon-β during acute phase.

Renato Antônio Dos Santos Oliveira,Mayara Marques Carneiro Da Silva,Carlos Eduardo Calzavara-Silva,Patrícia Muniz Mendes Freire De Moura,Ernesto Torres De Azevedo Marques Júnior,Paulo Neves Baptista Filho,Laura Helena Vega Gonzales Gil,Ana Maria Silva,Marli Tenório Cordeiro

doi:10.1590/0074-02760150453

Abstract

Dengue is an acute febrile disease caused by the mosquito-borne dengue virus (DENV) that according to clinical manifestations can be classified as asymptomatic, mild or severe dengue. Severe dengue cases have been associated with an unbalanced immune response characterised by an over secretion of inflammatory cytokines. In the present study we measured type I interferon (IFN-I) transcript and circulating levels in primary and secondary DENV infected patients. We observed that dengue fever (DF) and dengue haemorrhagic fever (DHF) patients express IFN-I differently. While DF and DHF patients express interferon-α similarly (52,71 ± 7,40 and 49,05 ± 7,70, respectively), IFN- β were associated with primary DHF patients. On the other hand, secondary DHF patients were not able to secrete large amounts of IFN- β which in turn may have influenced the high-level of viraemia. Our results suggest that, in patients from our cohort, infection by DENV serotype 3 elicits an innate response characterised by higher levels of IFN- β in the DHF patients with primary infection, which could contribute to control infection evidenced by the low-level of viraemia in these patients. The present findings may contribute to shed light in the role of innate immune response in dengue pathogenesis.

Highlights

Dengue is an acute febrile disease caused by the mosquito-borne dengue virus (DENV) that according to clinical manifestations can be classified as asymptomatic, mild or severe dengue
Clinical characteristics of DENV-infected patients 104 patients (46% men and 54% women) with acute dengue infection were included in the present study, of which 48 (46%) were classified as dengue fever (DF) and 56 (54%) as dengue haemorrhagic fever (DHF)
Age and gender of DF and DHF groups were similar with no significant difference between their medians

Summary

Introduction

Dengue is an acute febrile disease caused by the mosquito-borne dengue virus (DENV) that according to clinical manifestations can be classified as asymptomatic, mild or severe dengue. The antibody-dependent enhancement (ADE), proposes that DHF could be a consequence of an unbalanced immune response mediated by non-neutralising antibodies (Halstead & O’Rourke 1977, Halstead 1988) This condition would be characterised by increased monocyte activation and secretion of chemical mediators and pro-inflammatory cytokines (Green & Rothman 2006, Kurane 2007). The type I IFN secreted by virus infected cells acts in an paracrine and autocrine manner, through the binding to surface receptors initiating a signaling cascade through the JAK/STAT pathway which ends up regulating the expression of interferon-induced genes (ISG) These genes encode proteins that promote an “antiviral” state in both infected and non-infected cells, which inhibits the virus life cycle, hampering its spreading (Samuel 2001). The differences on IFN-b levels observed could lead to altered immune response which may play an important role on dengue pathogenesis

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Conclusion