Differential Proteomic Profiling at Different Phases of Dengue Infection: An Intricate Insight from Proteins to Pathogenesis

Dengue fever is a rapidly emerging
tropical disease and
an important
cause of morbidity in its severe form worldwide. A wide spectrum of
the pathophysiology is associated with the transition of dengue fever
to severe dengue, which is driven by the host immune response and
might reflect in patients’ proteome profile. This study aims
to analyze the plasma from different phases of dengue-infected patients
at two time points. A mass-spectrometry-based proteomic approach was
utilized to understand the involvement of probable candidate proteins
toward developing a more severe, hemorrhagic form of dengue fever.
Dengue-infected hospital-admitted patients with <5 days of fever
were included in this study. Patient samples from the acute phase
were screened for the presence of NS1 antigen using ELISA and subjected
to molecular serotyping. Dengue molecular serotype-confirmed patient
samples, pairwise from acute and critical phases with healthy control
were subjected to qualitative and quantitative proteomic analysis,
and then pathway analysis was performed. The protein–protein
interaction network between the dengue virus and host proteins was
depicted in the search for proteins associated with severe dengue
pathophysiology. An array of apolipoprotein, cytokines, and endothelial
proteins in association with virus replication and endothelial dysfunction
were validated as biomolecules involved in severe dengue pathophysiology.