Children with a higher RSV genomic load had a higher risk for more-severe bronchiolitis.

Viral respiratory infections are the most frequent cause of hospital admission for infants and young children during winter. However, the mechanisms of illness that are associated with viral lower-respiratory-tract infection (LRI) are unclear. A widely accepted hypothesis attributes the pathogenesis of viral LRI in infants to the induction of innate inflammatory responses. This theory is supported by studies showing that Toll-like receptor 4 is activated by respiratory syncytial virus (RSV), leading to production of inflammatory cytokines. We prospectively examined previously naive infants in Buenos Aires, Argentina, who had either upper- or lower-respiratory-tract symptoms. Infection with human metapneumovirus (hMPV) was second only to RSV in frequency. Both viruses were associated with rhinorrhea, cough, and wheezing; however, hMPV elicited significantly lower levels of respiratory inflammatory cytokines than did RSV. Symptoms in infants infected with influenza virus were different from those in infants infected with RSV, but cytokine responses were similar. These findings suggest that hMPV and RSV either cause disease via different mechanisms or share a common mechanism that is distinct from innate immune activation.

The attachment protein (glycoprotein) of respiratory syncytial virus (RSV) has long been associated with disease potentiation and respiratory symptoms. The glycoprotein has a conserved cysteinerich region (GCRR) whose function is unknown and which is not necessary for efficient viral replication. In this report, we show that the GCRR is a powerful inhibitor of the innate immune response against RSV, and that early secretion of glycoprotein is critical to modulate inflammation after RSV infection. Importantly, the GCRR is also a potent inhibitor of cytokine production mediated by several TLR agonists, indicating that this peptide sequence displays broad antiinflammatory properties. These findings have important implications for RSV pathogenesis and describe an inhibitor of TLR-mediated inflammatory responses that could have clinical applications.glycoprotein ͉ innate immunity ͉ Toll-like receptor 4