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Viruses. 2015 Feb 10;7(2):559-89. doi: 10.3390/v7020559.

Elevated cytokines, thrombin and PAI-1 in severe HCPS patients due to Sin Nombre virus.

Author information

1
Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA. vbondu@salud.unm.edu.
2
Clinical and Translational Science Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. rschrader@salud.unm.edu.
3
Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10031, USA. mag4@columbia.edu.
4
Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA. pmcguire@salud.unm.edu.
5
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-5644, USA. dlawrenc@med.umich.edu.
6
Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA. bhjelle@salud.unm.edu.
7
Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA. buranda@unm.edu.

Abstract

Sin Nombre Hantavirus (SNV, Bunyaviridae Hantavirus) is a Category A pathogen that causes Hantavirus Cardiopulmonary Syndrome (HCPS) with case fatality ratios generally ranging from 30% to 50%. HCPS is characterized by vascular leakage due to dysregulation of the endothelial barrier function. The loss of vascular integrity results in non-cardiogenic pulmonary edema, shock, multi-organ failure and death. Using Electric Cell-substrate Impedance Sensing (ECIS) measurements, we found that plasma samples drawn from University of New Mexico Hospital patients with serologically-confirmed HCPS, induce loss of cell-cell adhesion in confluent epithelial and endothelial cell monolayers grown in ECIS cultureware. We show that the loss of cell-cell adhesion is sensitive to both thrombin and plasmin inhibitors in mild cases, and to thrombin only inhibition in severe cases, suggesting an increasing prothrombotic state with disease severity. A proteomic profile (2D gel electrophoresis and mass spectrometry) of HCPS plasma samples in our cohort revealed robust antifibrinolytic activity among terminal case patients. The prothrombotic activity is highlighted by acute ≥30 to >100 fold increases in active plasminogen activator inhibitor (PAI-1) which, preceded death of the subjects within 48 h. Taken together, this suggests that PAI-1 might be a response to the severe pathology as it is expected to reduce plasmin activity and possibly thrombin activity in the terminal patients.

PMID:
25674766
PMCID:
PMC4353904
DOI:
10.3390/v7020559
[Indexed for MEDLINE]
Free PMC Article
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