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Viruses 2015, 7(2), 559-589; doi:10.3390/v7020559

Elevated Cytokines, Thrombin and PAI-1 in Severe HCPS Patients Due to Sin Nombre Virus

1
Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
2
Clinical and Translational Science Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
3
Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10031, USA
4
Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
5
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-5644, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Eric O. Freed
Received: 6 November 2014 / Accepted: 3 February 2015 / Published: 10 February 2015
(This article belongs to the Section Animal Viruses)
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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. View Full-Text
Keywords: hantavirus; PAI-1; ECIS; cell barrier function; hemostasis; proteomics hantavirus; PAI-1; ECIS; cell barrier function; hemostasis; proteomics
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Bondu, V.; Schrader, R.; Gawinowicz, M.A.; McGuire, P.; Lawrence, D.A.; Hjelle, B.; Buranda, T. Elevated Cytokines, Thrombin and PAI-1 in Severe HCPS Patients Due to Sin Nombre Virus. Viruses 2015, 7, 559-589.

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