A Polymorphism in the Catalase Gene Promoter Confers Protection against Severe RSV Bronchiolitis.

Jeffrey M Chambliss,Antonella Casola,John P Kelley,Maria Ansar,Heidi Spratt,Roberto P Garofalo

doi:10.3390/v12010057

Abstract

Respiratory syncytial virus (RSV) infection is associated with oxidative lung injury, decreased levels of antioxidant enzymes (AOEs), and the degradation of the transcription factor NF-E2-related factor 2 (NRF2), a master regulator of AOE expression. Single nucleotide polymorphisms (SNPs) in AOE and NRF2 genes have been associated with various lung disorders. To test whether specific NRF2 and/or AOE gene SNPs in children with RSV lower respiratory tract infection were associated with disease severity, one hundred and forty one children <24 month of age with bronchiolitis were assessed for seven AOE and two NRF2 SNPs, and data were correlated with disease severity, which was determined by need of oxygen supplementation and intensive care support. One SNP in the promoter region of the catalase gene, rs1001179, which is associated with higher enzyme expression, was significantly underrepresented (p = 0.01, OR 0.38) among patients with moderate to severe RSV bronchiolitis, suggesting a protective effect against disease severity. Our results suggest that increasing catalase expression/activity could exert a protective role in the context of RSV infection and represent a potential novel therapeutic target to ameliorate viral-induced lung disease.

Highlights

Respiratory syncytial virus (RSV) bronchiolitis remains one of the most common respiratory infections in infants and young children
Catalase Single nucleotide polymorphisms (SNPs) rs1001179 is protective against RSV severe disease
A total of 136 patients with RSV-positive lower respiratory tract infections (LRTI) were genotyped for seven antioxidant enzymes (AOEs) and two NF-E2-related factor 2 (NRF2) SNPs, which were selected based on their potential association with lung diseases (Table 2)

Summary

Introduction

Respiratory syncytial virus (RSV) bronchiolitis remains one of the most common respiratory infections in infants and young children. It resulted in an estimated 33.1 million cases of lower respiratory tract infection (LRTIs) globally in 2015, accounting for 3.2 million hospital admissions children [1]. Our understanding of the underlying molecular mechanisms that are responsible for RSV lower respiratory tract disease is still incomplete and remains a critical need to improve patient care and outcomes. Previous work in our laboratory has shown that RSV infection is associated with increased reactive oxygen species (ROS) production, leading to transcription factor activation and chemokine gene expression [4,5]. The transcription factor NF-E2-related factor 2 (NRF2), which binds the antioxidant response element (ARE) present in the promoter region of antioxidant enzymes

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