Project Details

Nasal response to rhinovirus infection in early childhood

Lillian Juttukonda, MD, PhD

Summary

BACKGROUND: Rhinovirus infections are common and cause a range of respiratory viral illnesses in children, including upper respiratory tract infections (URIs), lower respiratory tract infections (LRTIs), and rhinovirus-triggered wheezing. There are no vaccines or targeted therapies for rhinovirus infection, and development of such treatments is limited by the limited knowledge of the biological underpinnings driving different infectious outcomes. GAP: What are the protective and detrimental host responses to rhinovirus infection that define distinct rhinovirus disease phenotypes in infants and young children? HYPOTHESIS: Rhinovirus-induced wheezing or severe LRTI is secondary to a muted cell-intrinsic antiviral responses that result in aberrant induction of Type 2 immunity, which characterizes allergic inflammation. METHODS: We will perform and analyze scRNA-seq, bulk RNA-seq, antibody quantification, and viral sequencing on cryopreserved nasal swab samples from patients with rhinovirus URIs, rhinovirus-induced wheezing, severe rhinovirus LRTI requiring admission, or age-matched controls. Infants and children between 0-3 years of age who presented to the Emergency Department (ED) or Neonatal Intensive Care Unit (NICU) with respiratory symptoms and in whom laboratory testing revealed a qRT-PCR positive rhinovirus infection or age-matched controls who presented to the ED or NICU for non-respiratory symptoms. RESULTS: Pending. IMPACT: By elucidating the nasal cellular and transcriptional differences during rhinovirus infection between young children with URIs compared to children with rhinovirus-induced wheezing and severe LRTI, we may undercover cellular or molecular targets for therapeutic intervention.