Dengue virus binding and replication by platelets

Simon, A.Y., Sutherland, M.R. & Pryzdial, E.L. Blood 126, 378-385 (2015).

Speaker: Martyr Yang （楊俊常）                             Time: 13:00~14:00, Dec. 2, 2015

Commentator: Dr. Trai-Ming Yeh (葉才明博士)         Place: Room 601

Abstract：

Dengue virus (DENV) is a positive-sense, single-stranded ((+)ss) RNA virus of the family Flaviviridae which infects about 390 million people per year. More than half of the DENV-infected people are asymptomatic, while the rest of them are self-limited dengue fever (DF) and about 500,000 are life-threatening dengue hemorrahagic fever (DHF) or dengue shock syndrome (DSS) ^[1]. Both mild and severe DENV infections cause thrombocytopenia in patients. Impaired thrombopoiesis, platelet–leukocyte interactions and autoimmune-induced platelet clearance are the known mechanisms of thrombocytopenia ^[2]. However, the direct interaction between virus and platelet in primary infection has not been ascertained. In this study, bound DENV particles on platelet were investigated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). At 37°C, 800 virus particles specifically bound to a platelet, but fewer particles were observed at 25°C (~350) and even lesser at 4°C (~200) through electron microscopy. The treatment of anti-dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin (DC-SIGN) antibody or low-molecular weight heparin (LMWH) proved that DC-SIGN and heparan sulfate proteoglycan (HSP) are DENV receptors on platelet. In addition, DENV genome replicated in platelets up to ~4-fold over 7 days at both 25°C (blood bank storage temperature) and 37°C (physiological temperature). Furthermore, DENV NS1 protein increased over the 7-day experimental period indicating the replication of virus. Moreover, cyclohexamide treatment caused the platelets being incapable of replicating the DENV genome. These data proclaim that DENV can bind platelets directly and then replicate to produce infectious virus. In conclusion, platelets participate in the pathogenesis of DENV and may be a short-term carrier of DENV virus. This may be a new consideration in the mechanisms of DENV-induced thrombocytopenia.

References:

1) Bhatt S, Gething PW, Brady OJ, et.al. The global distribution and burden of dengue. Nature 496, 504-507 (2013).

2) Hottz E, Tolley ND, Zimmerman GA, et.al. Platelets in dengue infection. Haematology 8, e33-e38 (2011).