Serum Proteome Changes in Dengue Virus-Infected Patients from a Dengue-Endemic Area of India: Towards New Molecular Targets?

Abstract

The global burden of dengue continues to worsen, specifically in tropical and subtropical countries, and has evolved as a major public health problem. We investigated the changes in serum proteome in dengue fever (DF) patients from a dengue-endemic area of India to obtain mechanistic insights about the disease pathogenesis, the host immune response, and identification of potential serum protein biomarkers of this infectious disease. In this study, serum samples from DF patients, healthy subjects, and patients with falciparum malaria (an infectious disease control) were investigated by 2D-DIGE in combination with MALDI-TOF/TOF MS. The findings were validated with Western blotting. Functional clustering of the identified proteins was performed using PANTHER and DAVID tools. Compared to the healthy controls, we found significant changes in the expression levels of 48 protein spots corresponding to 18 unique proteins (7 downregulated and 11 upregulated) in DF patients (p<0.05). Among these differentially-expressed proteins, 11 candidates exhibited different trends in dengue fever compared to falciparum malaria. Importantly, our results suggest that dengue virus infection leads to alterations in expression levels of multiple serum proteins involved in diverse and vital physiological pathways, including acute phase response signaling, complement cascades, hemostasis, and blood coagulation. For the first time we report here that the serum levels of hemopexin, haptoglobin, serum amyloid P, and kininogen precursor, are altered in DF. This study informs the pathogenesis and host immune response to dengue virus infection, as well as the current search for new diagnostic and molecular drug targets.

Discovery and Characterization of Potential Prognostic Biomarkers for Dengue Hemorrhagic Fever

“…The Hx and Tf require further analysis to determine why our data differed from other researchers. 17,28,29 After further characterization of Vtn, Hx, and Tf, we may find that a combination of biomarkers has the greatest utility as a prognostic test for severe dengue as noted by other researchers. 7 Vitronectin is a multifunctional glycoprotein that circulates in the blood, usually as an inactive monomer, until it is recruited to regulate coagulation and platelet aggregation.…”

“…Our healthy controls had 2-fold higher Hx (1,571 μg/mL) compared with a previous report (770 μg/mL). 40 Ray and colleagues 28 observed higher Hx levels in healthy controls compared with DF. This discrepancy could be caused by a difference in methods (Western blot versus ELISA), or to sample size (HC = 6, DF = 6).…”

Proteomic analysis reveals the enhancement of human serum apolipoprotein A‐1(APO A‐1) in individuals infected with multiple dengue virus serotypes

“…The serum was separated from blood (2 ml) by centrifugation at 3000 g for 10 min in a microfuge tube. Blood sample collection, serum separation and processing were performed as per the description .…”

High-resolution proteomics identifies potential new markers of Zika and dengue infections

“…The 7 proteins with higher expression values in DENV vs. ZIKV include VTI1B, a protein involved in SNARE mediated vesicle transport. Many of the proteins have known relationships to either DENV and ZIKV infections: interestingly, 5 of the differentially expressed proteins have also been identified in an independent proteomic study comparing dengue patients to healthy controls (C3, C4, HP, HPX, and ITIH4) 11 . Further, with just a few exceptions, all 26 proteins had some relationship to pregnancy, often related to pre-eclampsia, and regulation of brain function ( Table 2, Supplementary Table S5).…”