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Open AccessArticle

Deletions in Genes Participating in Innate Immune Response Modify the Clinical Course of Andes Orthohantavirus Infection

1
Programa Hantavirus, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Av. La Plaza 680, Las Condes, Región Metropolitana 7500000, Chile
2
Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Pedro de Valdivia 425, Región Metropolitana 7500000, Santiago, Chile
3
Departamento Pediatria Clinica Alemana de Santiago, Av Vitacura 5951, Vitacura, Región Metropolitana 7500000, Chile
4
Departamento de Enfermedades Infecciosas e Inmunología Pediátricas, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Región Metropolitana 7500000, Chile
5
Department of Internal Medicine, MSC10 5550, 1 University of New Mexico, Albuquerque, NM 87131-0001, USA
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(8), 680; https://doi.org/10.3390/v11080680
Received: 31 May 2019 / Revised: 28 June 2019 / Accepted: 9 July 2019 / Published: 25 July 2019
(This article belongs to the Special Issue Hantaviruses)
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PDF [1949 KB, uploaded 25 July 2019]
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Abstract

Andes orthohantavirus (ANDV) is an important human pathogen causing hantavirus cardiopulmonary syndrome (HCPS) with a fatality rate of 30% in Chile. Around 60% of all cases have a severe clinical course, while the others have a mild clinical course. The main goal of this study was to understand if the genetic variation of patients is associated with the clinical course they develop after ANDV infection. For this, the frequency of copy number variants (CNVs, i.e., deletions and duplications) was studied in 195 patients, 88 with mild and 107 with severe HCPS. CNVs were called from intensity data of the Affymetrix Genome-Wide SNP Array 6.0. The analysis of the data was performed with PennCNV, ParseCNV and R softwares; Results: a deletion of 19, 416 bp in the q31.3 region of chromosome 1 is found more frequently in severe patients (p < 0.05). This region contains Complement Factor H Related (CFHR1) and CFHR3 genes, regulators of the complement cascade. A second deletion of 1.81 kb located in the p13 region of chr20 was significantly more frequent in mild patients (p < 0.05). This region contains the SIRPB1 gene, which participates in the innate immune response, more specifically in neutrophil trans-epithelial migration. Both deletions are associated with the clinical course of HCPS, the first being a risk factor and the second being protective. The participation of genes contained in both deletions in ANDV infection pathophysiology deserves further investigation. View Full-Text
Keywords: HCPS; ANDV; hantavirus HCPS; ANDV; hantavirus
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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

Ribeiro, G.E.; Leon, L.E.; Perez, R.; Cuiza, A.; Vial, P.A.; Ferres, M.; Mertz, G.J.; Vial, C. Deletions in Genes Participating in Innate Immune Response Modify the Clinical Course of Andes Orthohantavirus Infection. Viruses 2019, 11, 680.

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