Abstract
Dengue virus, a mosquito-borne flavivirus, is a causative agent for dengue infection, which manifests with symptoms ranging from mild fever to fatal dengue shock syndrome. The presence of four serotypes, against which immune cross-protection is short-lived and serotype cross-reactive antibodies that might enhance infection, pose a challenge to further investigate the role of virus and immune response in pathogenesis. We evaluated the viral and immunological factors that correlate with severe dengue disease in a cohort of pediatric dengue patients in New Delhi. Severe dengue disease was observed in both primary and secondary infections. Viral load had no association with disease severity but high viral load correlated with prolonged thrombocytopenia and delayed recovery. Severe dengue cases had low Th1 cytokines and a concurrent increase in the inflammatory mediators such as IL-6, IL-8 and IL-10. A transient increase in CD14+CD16+ intermediate monocytes was observed early in infection. Sorting of monocytes from dengue patient peripheral blood mononuclear cells revealed that it is the CD14+ cells, but not the CD16+ or the T or B cells, that were infected with dengue virus and were major producers of IL-10. Using the Boruta algorithm, reduced interferon-α levels and enhanced aforementioned pro-inflammatory cytokines were identified as some of the distinctive markers of severe dengue. Furthermore, the reduction in the levels of IL-8 and IL-10 were identified as the most significant markers of recovery from severe disease. Our results provide further insights into the immune response of children to primary and secondary dengue infection and help us to understand the complex interplay between the intrinsic factors in dengue pathogenesis.
Highlights
Dengue virus (DENV) infects close to 390 million people every year of which about 96 million have clinical manifestations that range from undifferentiated febrile illness to fatal shock syndrome [1]
The role of dengue virus levels in the blood and the kinetics of infection and immune response that results in severe dengue disease in humans is not well characterized
We analyzed 97 children with varying degrees of dengue disease, and we show that the dengue virus quantity in blood does not show any significant association with severe disease
Summary
Dengue virus (DENV) infects close to 390 million people every year of which about 96 million have clinical manifestations that range from undifferentiated febrile illness to fatal shock syndrome [1]. One of the mechanisms attributed to severe infections is antibody-dependent enhancement (ADE), wherein subneutralizing antibodies against primary infecting serotype bind, but do not neutralize the heterologous infecting serotype. There are contradictory findings from various groups regarding the secreted markers of disease progression and or severity and the role of dengue viremia in pathogenesis [6,7,8,9,10,11]. Most of these studies have been reported from tropical and sub-tropical regions of the world including South America, South- and South-East Asia. Our findings may help in understanding the molecular mechanism of the interaction between the virus and the host immune response that culminate in severe dengue disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
