Research Projects

Dengue (DV) infection cause notable morbidity and mortality and are recognized as important pathogens in India. However, it is not clear what molecular triggers cause severity. The immunopathogenic mechanisms that drive disease progression are ill-understood. Our previous RNA-seq study (Translational Research, 2017) as well as studies reported by others, pointed towards uncontrolled neutrophil activation and related genes associated with development of dengue severity. Uncontrolled neutrophil activation may be the due to phenotypic changes occurs during direct interaction with the viruses or it may arise due to defect in haematopoiesis process. Dengue virus is known to infect hematopoietic stem cells as well as stromal cells in bone marrow. However, there is a gap in understanding whether dengue infection causes defect in haematopoiesis triggering uncontrolled myeloid differentiation. Thus, a detailed study to delineate the impact of dengue virus on haematopoiesis and neutrophil biogenesis is warranted. Therefore, we propose to study the molecular events happening in the bone marrow during dengue infection and understand the mechanisms of uncontrolled neutrophil activation. In this project, we are proposing to use ex vivo bone marrow progenitor cells expansion model, Human hematopoietic progenitor stem cells, DV infected experimental animal model and human promyelocytes cell line (HL-60) to delineate the role of DV in myeloid cell differentiation. To understand complex interactions between virus and host immune cells, we have proposed the following objectives. Objective 1: To study the effect of dengue infection in haematopoiesis process in bone marrow. Objective 2: To identify the factors that modulate myeloid cell differentiation during dengue virus infection Objective 3: To study the functional consequences of dengue virus infection on neutrophils phenotypes and functions We hope that at the end of the project, we will be able to know the molecular and cellular events that regulate emergency granulopoiesis during dengue disease progression. Also, we will be able to see at what level dengue virus induces defect in haematopoiesis process.

Neutrophil phenotype, Dengue, haematopoiesis, granulopoiesis