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

Journal
Viruses
ISSN
1999-4915
Date Issued
2019
Author(s)
Grazielle Esteves Ribeiro
Luis Edgardo Leon
Ruth Perez
Analia Cuiza
Marcela Ferres
Gregory J. Mertz
Type
Resource Types::text::journal::journal article
Scopus ID
2-s2.0-85070093772
WoS ID
WOS:000482993900039
DOI
URL
URL Institutional Repository
Abstract
<jats:p>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.</jats:p>
Cite this document
Ribeiro, G. E., Leon, L. E., Perez, R., Cuiza, A., Vial, P. A., Ferres, M., Mertz, G. J., & Vial, C. (2019). Deletions in genes participating in innate immune response modify the clinical course of andes orthohantavirus infection. Viruses, 11(8), 680. https://doi.org/10.3390/v11080680
Project(s)
Subjects
hcps

; 

andv

; 

hantavirus

; 

aged

; 

chile

; 

complement factor h

; 

dna copy number variations

; 

female

; 

genetic predisposition to disease

; 

genetic variation

; 

genotype

; 

hantavirus

; 

hantavirus infections

; 

humans

; 

immunity, innate

; 

male

; 

middle aged

; 

oligonucleotide array sequence analysis

; 

prospective studies

; 

receptors, cell surface

; 

sequence deletion

; 

complement factor h

; 

genomic dna

; 

cell surface receptor

; 

sirpb1 protein, human

; 

adult

; 

allele

; 

article

; 

artificial ventilation

; 

chromosome 1

; 

clinical outcome

; 

copy number variation

; 

disease course

; 

disease severity

; 

dna extraction

; 

female

; 

gene

; 

gene deletion

; 

gene frequency

; 

gene mapping

; 

genetic variation

; 

genome-wide association study

; 

genotype

; 

hantavirus

; 

hantavirus pulmonary syndrome

; 

human

; 

immune response

; 

innate immunity

; 

major clinical study

; 

male

; 

nonhuman

; 

orthohantavirus

; 

pathophysiology

; 

risk factor

; 

rna virus

; 

sirpb1 gene

; 

transendothelial and transepithelial migration

; 

aged

; 

chile

; 

dna microarray

; 

genetic predisposition

; 

genetics

; 

hantavirus infection

; 

immunology

; 

middle aged

; 

prospective study