Deletions in Genes Participating in Innate Immune Response Modify the Clinical Course of Andes Orthohantavirus Infection
Grazielle Esteves Ribeiro,
Luis Edgardo Leon,
Ruth Perez,
Analia Cuiza,
Pablo Agustin Vial,
Marcela Ferres,
Gregory J. Mertz,
Cecilia Vial
Affiliations
Grazielle Esteves Ribeiro
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
Luis Edgardo Leon
Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Pedro de Valdivia 425, Región Metropolitana 7500000, Santiago, Chile
Ruth Perez
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
Analia Cuiza
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
Pablo Agustin Vial
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
Marcela Ferres
Departamento de Enfermedades Infecciosas e Inmunología Pediátricas, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Región Metropolitana 7500000, Chile
Gregory J. Mertz
Department of Internal Medicine, MSC10 5550, 1 University of New Mexico, Albuquerque, NM 87131-0001, USA
Cecilia Vial
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
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.
