WIP 141 - Nasal Response to Rhinovirus Infection in Early Childhood by single-cell RNA sequencing

Poster Number: WIP 141
Publication Number: WIP 141.944

Background: Human rhinovirus (HRV) is the most common respiratory virus. HRV frequently causes upper respiratory tract infections (URI), but HRV also causes lower respiratory tract infections and is the leading trigger of wheezing in young children. Importantly, HRV-triggered wheezing in toddlers is strongly associated with childhood asthma. No vaccines or antibody prophylactic therapies exist to prevent HRV infections. However, it is not known whether different clinical responses to HRV infection are driven by distinct host responses. The respiratory epithelium within the nasal mucosa is the site of primary HRV replication; thus, we posit that distinct host responses to HRV in the nasal mucosa will be reflective of differing clinical phenotypes. By elucidating HRV-induced cellular and transcriptional responses within the nasal mucosa of young children with different disease phenotypes, we will uncover pathways involved in disease pathogenesis.

Objective: To investigate the host response to HRV infection within the nasal mucosa of infants and toddlers using single-cell RNA sequencing (scRNA-seq). We will examine how the cellular and transcriptional landscape differs between patients with and without wheeze and identify cell-intrinsic and bystander responses to HRV infection.

Design/Methods: We are performing scRNA-seq, bulk RNA-seq, antibody quantification, and viral sequencing on cryopreserved nasal swab samples obtained from patients 0-3 years of age who presented to the Emergency Department (ED) with viral respiratory symptoms and were found to be HRV+, or age-matched controls who presented for mild traumatic injury. The study is IRB approved, sample collection and sequencing is completed (n = 46), and analysis will be completed by the spring of 2024. The cohort is stratified into patients with URIs without wheeze, discharged or admitted patients with wheeze, and controls. Our primary outcome of interest is the cellular composition and differential gene expression of the nasal tissue in the different groups, as well as the identity and behavior of HRV-infected cells.