Abstract
Dengue is an important infectious disease that presents high incidence and yields a relevant number of fatal cases (about 20,000) every year worldwide. Despite its epidemiological relevance, there are many knowledge gaps concerning dengue pathogenesis, especially with regards to the circumstances that drive a mild clinical course to a severe disease. In this work, we investigated the participation of high mobility group box 1 (HMGB1), an important modulator of inflammation, in dengue fatal cases. Histopathological and ultrastructural analyses revealed that liver, lung and heart post-mortem samples were marked by tissue abnormalities, such as necrosis and apoptotic cell death. These observations go in line with an HMGB1-mediated response and raised concerns regarding the participation of this cytokine in promoting/perpetuating inflammation in severe dengue. Further experiments of immunohistochemistry (IHC) showed increased expression of cytoplasmic HMGB1 in dengue-extracted tissues when compared to non-dengue controls. Co-staining of DENV RNA and HMGB1 in the host cell cytoplasm, as found by in situ hybridization and IHC, confirmed the virus specific induction of the HMGB1-mediated response in these peripheral tissues. This report brings the first in-situ evidence of the participation of HMGB1 in severe dengue and highlights novel considerations in the development of dengue immunopathogenesis.
Highlights
Dengue is a mild flu-like mosquito-borne illness which presents a small chance of evolving into life-threatening forms[1]
Regarding the dynamics of high motility group box 1 (HMGB1) translocation in cell death, it is known that this protein can readily move outside the cell when membrane integrity is lost during necrosis[42]
When HMGB1 is found in the cell cytoplasm, it suggests its release to the extracellular environment either by passive or active processes
Summary
Dengue is a mild flu-like mosquito-borne illness which presents a small chance (about 5%) of evolving into life-threatening forms[1]. Conventional clinical manifestations of dengue (fever, myalgia and headaches) occur during high viremia, DHF/DSS takes place after the abatement of fever and virus elimination from the circulation These observations led to the idea that severe dengue may be developed under an immunopathological basis[4,5]. DAMPs, known as alarmins, are host biomolecules that can signal to initiate and perpetuate an inflammatory response[18] One of these molecules that has drawn attention in virus research is the high motility group box 1 (HMGB1) due to its association to disease severity in dengue[19] and in other viral infections[20,21,22]. Our data highlights the relevance of this cytokine in dengue and brings new considerations concerning the immunopathogenesis of the 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 call
