Respiratory syncytial virus and asthma: speed-dating or long-term relationship?

Abstract

Purpose of review: Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children worldwide. Furthermore, epidemiological evidence has been accumulating that RSV lower respiratory tract infection in infants may be linked to subsequent development of recurrent wheezing and asthma in childhood. This article reviews the epidemiological evidence linking RSV and asthma and some new hypotheses of the cellular and molecular mechanisms of postviral airway inflammation and hyperreactivity that have been proposed to explain the epidemiological link.

Recent findings: New epidemiological studies have suggested that viral pathogens other than RSV, especially human rhinoviruses (HRV), may play an important role in the inception of atopic asthma. Also, recent experimental evidence is challenging the widely accepted axiom that RSV is cleared from immunocompetent hosts within weeks from the onset of the infection. In particular, bone marrow stromal cells may be a frequent target of human RSV infection, develop structural and functional changes when infected, participate actively in the pathogenesis of the acute disease, and harbor the virus chronically, allowing persistence of the infection.

Summary: RSV - and possibly other common respiratory pathogens - play an important role not only in the exacerbation, but also in the inception of asthma. The latter effect may involve the persistence of latent virus in extrapulmonary tissues, similar to what has been recently found for some bacterial species. The most immediate consequence of these discoveries is that future prophylactic and therapeutic strategies for common infections caused by viral or bacterial pathogens may have to address the coverage of remote sites of latent persistence or replication, in order to avoid chronic sequelae-recurrent wheezing and asthma.

Figure 1. Model of RSV Persistence

RSV silences miR-221 expression in epithelial cells. The consequent upregulation of the NGF-TrKA axis not only potentiates the local nociceptive innervation and neurogenic inflammation in distal airways, but also functions as a critical virulence mechanism implemented by RSV to coax host cells to resist apoptosis and persist latently in the lungs, and/or in a safe extra-pulmonary niche within the bone marrow mesenchyme where it avoids detection from the immune system. Persistence of RSV virions and chronic upregulation of the NGF-TrKA axis may turn on lytic replication and inflammation in response to viral reinfection or reactivation, contributing to persistent airway hyperreactivity (AHR) and obstructive lung disease.