title: Platelet activation determines the severity of thrombocytopenia in dengue infection.
abstract: Thrombocytopenia is common in patients with dengue virus (DENV) infections. With a focus on understanding the possible mechanism of thrombocytopenia in DENV infections we described a direct correlation between activation and depletion of platelets in patients. Our data showed a sharp decrease in platelet counts at day 4 of fever in patients. The high DENV genome copies in platelets correlated directly with the elevated platelet activation along with increased binding of complement factor C3 and IgG on their surface at day 4. Recovery in platelet count was observed on day 10 through day 6 and 8 with simultaneous decrease in platelet activation markers. Further, our in vitro data supported the above observations describing a concentration-dependent increase in platelet activation by DENV serotype-2. The high copy number of DENV2 genome in the platelet pellet correlated directly with platelet activation, microparticle generation and clot formation. Furthermore the DENV2-activated platelets were phagocytosed in large numbers by the monocytes. The DENV2-mediated lysis and clearance of platelets were abrogated in presence of platelet activation inhibitor, prostacyclin. These observations collectively suggest that platelet activation status is an important determinant of thrombocytopenia in dengue infections. A careful strategy of inactivation of platelets may rescue them from rapid destruction during DENV infections.
authors.affiliation: Disease Biology Laboratory, Regional Centre for Biotechnology, National Capital Region Biotech Science Cluster, Faridabad, India.|Department of Biotechnology, Manipal University, Karnataka, India.
authors.forename: Amrita
authors.initials: A
authors.lastname: Ojha
authors.affiliation: Disease Biology Laboratory, Regional Centre for Biotechnology, National Capital Region Biotech Science Cluster, Faridabad, India.
authors.forename: Dipika
authors.initials: D
authors.lastname: Nandi
authors.affiliation: Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, National Capital Region Biotech Science Cluster, Faridabad, India.
authors.forename: Harish
authors.initials: H
authors.lastname: Batra
authors.affiliation: Disease Biology Laboratory, Regional Centre for Biotechnology, National Capital Region Biotech Science Cluster, Faridabad, India.|Department of Biotechnology, Manipal University, Karnataka, India.
authors.forename: Rashi
authors.initials: R
authors.lastname: Singhal
authors.affiliation: Disease Biology Laboratory, Regional Centre for Biotechnology, National Capital Region Biotech Science Cluster, Faridabad, India.|Department of Biotechnology, Manipal University, Karnataka, India.
authors.forename: Gowtham K
authors.initials: GK
authors.lastname: Annarapu
authors.affiliation: Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, National Capital Region Biotech Science Cluster, Faridabad, India.
authors.forename: Sankar
authors.initials: S
authors.lastname: Bhattacharyya
authors.affiliation: Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Tulika
authors.initials: T
authors.lastname: Seth
authors.affiliation: Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Lalit
authors.initials: L
authors.lastname: Dar
authors.affiliation: Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, National Capital Region Biotech Science Cluster, Faridabad, India.
authors.forename: Guruprasad R
authors.initials: GR
authors.lastname: Medigeshi
authors.affiliation: Vaccine and Infectious Disease Research Center, Translational Health Science and Technology Institute, National Capital Region Biotech Science Cluster, Faridabad, India.
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Vrati
authors.affiliation: Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Naval K
authors.initials: NK
authors.lastname: Vikram
authors.affiliation: Disease Biology Laboratory, Regional Centre for Biotechnology, National Capital Region Biotech Science Cluster, Faridabad, India.
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Guchhait
mesh_terms: D017209:Apoptosis / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism; D003715:Dengue / Q000150:complications* / Q000821:virology; D003716:Dengue Virus / Q000235:genetics; D016679:Genome, Viral; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D015539:Platelet Activation / Q000276:immunology; D010976:Platelet Count; D012720:Severity of Illness Index; D013921:Thrombocytopenia / Q000097:blood* / Q000175:diagnosis / Q000209:etiology*; D013927:Thrombosis / Q000276:immunology; D019562:Viral Load
chemical_list: D003176:Complement C3; D007074:Immunoglobulin G