Abstract
Dengue virus (DENV) is a human pathogen and its etiology has been widely established. There are many interactions between DENV and human proteins that have been reported in literature. However, no publicly accessible resource for efficiently retrieving the information is yet available. In this study, we mined all publicly available dengue–human interactions that have been reported in the literature into a database called DenHunt. We retrieved 682 direct interactions of human proteins with dengue viral components, 382 indirect interactions and 4120 differentially expressed human genes in dengue infected cell lines and patients. We have illustrated the importance of DenHunt by mapping the dengue–human interactions on to the host interactome and observed that the virus targets multiple host functional complexes of important cellular processes such as metabolism, immune system and signaling pathways suggesting a potential role of these interactions in viral pathogenesis. We also observed that 7 percent of the dengue virus interacting human proteins are also associated with other infectious and non-infectious diseases. Finally, the understanding that comes from such analyses could be used to design better strategies to counteract the diseases caused by dengue virus. The whole dataset has been catalogued in a searchable database, called DenHunt (http://proline.biochem.iisc.ernet.in/DenHunt/).
Highlights
Dengue, an emerging infectious disease, is presently the most common arboviral disease globally
The retrieved interactions were classified into three types: (i) Direct interactions, where the human proteins physically interact with the viral proteins or RNA, (ii) Indirect or functional interactions, where the human proteins affect viral replication but there exists no current evidence of them directly interacting with the viral components and (iii) Differentially expressed interactions, genes or proteins whose expression patterns are altered during dengue viral infection
All the graphical images for the pathways, which have 20 and more dengue interacting human proteins, belonging to signal transduction and immune systems categories are given in the S1 Fig. Here, we describe the role of two pathways, NF-κB and retinoic acid-inducible gene I (RIG-I)-like receptor signaling pathway, in viral infection (Fig 3)
Summary
An emerging infectious disease, is presently the most common arboviral disease globally. Dengue infection leads to complications ranging from mild dengue fever to more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). It is not fully understood why most patients clear dengue infections quickly without any complications, whereas others develop a potentially fatal vascular leakage syndrome or severe hemorrhages. The large size of the population prone to infection by dengue vouches for the importance of the development of vaccines for prevention and antiviral therapies to manage/treat dengue viral infections. Clinical diagnosis and careful clinical management by experienced physicians and nurses to increase survival of patients are still the most commonly used strategies to treat dengue infections
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