IFNL4 Genotypes Predict Clearance of RNA Viruses in Rwandan Children With Upper Respiratory Tract Infections

Abstract

Polymorphisms in the interferon lambda gene locus (<i>IFNL</i>) such as the <i>IFNL4</i> genetic variants <i>rs12979860</i> and <i>rs368234815</i> are predictive of resolution of hepatitis C virus infection, but information about the impact of these variants in other infections is scarce. This study aimed at determining the potential impact of <i>IFNL4</i> variation for the clearance of respiratory tract pathogens in Rwandan children (≤5 years old, <i>n</i> = 480) seeking medical care for acute respiratory infections. Nasopharyngeal swabs were retrieved from all children at the first hospital referral and from 161 children at follow-up visits 2 weeks later. The swabs were analyzed for pathogens by real-time PCR and for host cell <i>IFNL4</i> genotype at <i>rs12979860</i> and <i>rs368234815</i>. Approximately 1/3 of the children were homozygous for the <i>rs12979860</i> T allele and the <i>rs368234815</i> ΔG allele, which are overrepresented in subjects of African descent. These <i>IFNL4</i> variants were significantly associated with reduced clearance of RNA viruses. Our results suggest that <i>IFNL4</i> genotypes that are common among subjects of African descent may determine inefficacious clearance of RNA viruses from the respiratory tract.