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

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.

Prune-1 drives polarization of tumor-associated macrophages (TAMs) within the lung metastatic niche in triple-negative breast cancer

“…It was defined as one of the markers of cytolytic activity in the TME of TNBC, together with the mutation status of TP53 mut and PIK3CA wt (Cheng et al, 2020), thus acting as a marker for response to immunotherapy. On the other hand, Sirpb1b (or CD172B) shows strong correlations with immune system pathways that positively modulate the production of pro-inflammatory cytokines, including interleukin family cytokines, TNF-a, and GM-CSF (Huang et al, 2013), and participates in neutrophil trans-epithelial migration (Ribeiro et al, 2019). Of interest, the transcriptional factor SV140 is a master regulator that acts as a modulator of the adaptive immune response in BC.…”

Identification of m6A Regulator-Associated Methylation Modification Clusters and Immune Profiles in Melanoma

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Screening and identification of serum biomarkers of osteoarticular tuberculosis based on mass spectrometry

“…In addition, some studies have reported that deletion of CFHR1-related gene loci may lead to aggravation of pathogenic infections such as Andes orthohantavirus (ANDV) and Shiga toxin. 27,28 The main mechanism is that it mediates activation of the complement system, and the lack of this protein can cause the body to be unable to fully resist pathogen invasion. Furthermore, CFHR1…”