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Thromb Res. 2014 Aug;134(2):449-54. doi: 10.1016/j.thromres.2014.05.003. Epub 2014 May 14.

Elevated levels of full-length and thrombin-cleaved osteopontin during acute dengue virus infection are associated with coagulation abnormalities.

Author information

1
Division of Emerging Infectious Diseases, Department of Internal Medicine, Graduate School of Medicine; Laboratory of Disaster-related Infectious Disease, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
2
Department of Blood Borne Diseases, San Lazaro Hospital, Manila, Philippines.
3
Department of Tropical Medicine, John A. Burns School of Medicine, University of HI, Manoa, USA.
4
Medical Informatics Division, Takeda General Hospital, Kyoto, Japan.
5
National Reference Laboratory for HIV/AIDS, Hepatitis, and other STDs, STD/AIDS Cooperative Central Laboratory, Manila, Philippines.
6
Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
7
Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Japan.
8
Division of Emerging Infectious Diseases, Department of Internal Medicine, Graduate School of Medicine; Laboratory of Disaster-related Infectious Disease, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan. Electronic address: hatoriaoi@gmail.com.

Abstract

INTRODUCTION:

Dengue virus (DENV) is transmitted by the mosquito vector, and causes a wide range of symptoms that lead to dengue fever (DF) or life-threatening dengue hemorrhagic fever (DHF). The host and viral correlates that contribute to DF and DHF are complex and poorly understood, but appear to be linked to inflammation and impaired coagulation. Full-length osteopontin (FL-OPN), a glycoprotein, and its activated thrombin-cleaved product, trOPN, integrate multiple immunological signals through the induction of pro-inflammatory cytokines.

MATERIALS AND METHOD:

To understand the role of OPN in DENV-infection, we assessed circulating levels of FL-OPN, trOPN, and several coagulation markers (D-dimer, thrombin-antithrombin complex [TAT], thrombomodulin [TM], and ferritin in blood obtained from 65 DENV infected patients in the critical and recovery phases of DF and DHF during a dengue virus epidemic in the Philippines in 2010.

RESULTS:

Levels of FL-OPN, trOPN, D-dimer, TAT, and TM were significantly elevated in the critical phase in both the DF and DHF groups, as compared with healthy controls. During the recovery phase, FL-OPN levels declined while trOPN levels increased dramatically in both the DF and DHF groups. FL-OPN levels were directly correlated with D-dimer and ferritin levels, while the generation of trOPN was associated with TAT levels, platelet counts, and viral RNA load.

CONCLUSION:

Our study demonstrated the marked elevation of plasma levels of FL-OPN and thrombin-cleaved OPN product, trOPN, in DENV-infection for the first time. Further studies on the biological functions of these matricellular proteins in DENV-infection would clarify its pathogenesis.

KEYWORDS:

Coagulation; Dengue virus; Full-length osteopontin; Inflammation; Thrombin; Thrombin-cleaved osteopontin

PMID:
24861695
PMCID:
PMC4112014
DOI:
10.1016/j.thromres.2014.05.003
[Indexed for MEDLINE]
Free PMC Article
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