Transcriptomic characterization provides insights into Hantavirus Cardiopulmonary Syndrome (HCPS) severity
Date
2020
Type:
Thesis
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136 p.
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Authors
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Journal Title
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Publisher
Universidad del Desarrollo. Facultad de Medicina
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Abstract
Hantaviruses are important human pathogens that cause a severe zoonotic disease
called hantavirus cardiopulmonary syndrome (HCPS), presenting a case fatality rate up
to 40%. Clinical course of HCPS may present as a mild condition with moderate
respiratory failure or progress rapidly to a severe condition with cardiopulmonary shock
that can be fatal. However, the role of the host's responses in this progression towards
HCPS and their association with severity remains elusive. In this study, a transcriptome
approach combined with clinical laboratory data was applied to gain a better insight into
factors associated with HCPS severity. For this, total RNA was extracted from peripheral
blood mononuclear (PBMCs) isolated from hantavirus infected patients in acute and
convalescent phases. Healthy subjects were used as control. Severe patients are defined
as those who develop cardiopulmonary shock and need to receive vasoactive drugs and
mechanical ventilation as a treatment and in the most severe cases, they also receive
extracorporeal membrane oxygenation (ECMO). Mild clinical course is defined as a
disease characterized only by prodromal symptoms or who progress to a minor
cardiorespiratory failure that does not require mechanical ventilation and remains
hemodynamically stable. Samples from 18 patients (12 severe and 6 mild) and 9 healthy
controls were sequenced and analyzed. Differential expression was evaluated by
comparing the patient samples grouped by severity in acute and convalescent phase
versus the healthy controls. Our results showed that proprotein convertase subtilisin/kexin
type 9 (PCSK9) mRNA and serum levels are increased and could contribute to
proinflammatory response in severe HCPS patients. PCSK9 has two FDA approved
inhibitors and could be a potential therapeutic target for HCPS. Also showed that
hantaviruses can become insensitive to type I IFN response, which contributes to a more
severe HCPS outcome
Description
Thesis presented to the Faculty of Medicine Clinica Alemana-Universidad del Desarrollo
in order to apply for Doctoral degree (PhD) in Science and Innovation in Medicine
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Citation
Keywords
Hantavirus, SCPH, Transcriptome, HCPS, Andes virus, 090036S