Respiratory Syncytial Virus (RSV) infects nearly all children by their second birthday. RSV usually causes mild respiratory illness, however, a subset of patients experience severe infection that require hospitalization. Successful host defense against viral pathogens requires rapid recognition of the virus and activation of both innate and adaptive immunity. Toll-Like Receptors (TLRs) are responsible for mounting an innate immune response and genetic variations within TLRs modulate severity of infection. Researchers at NIEHS have identified a single nucleotide polymorphism (SNP) in TLR8 that is associated with RSV disease severity. The SNP is p53-responsive allele, indicating that p53, a master cell cycle regulator, can strongly influence TLR8 mediated immune responses. Identification of this SNP can inform diagnosis and prognosis of RSV disease and serve as a therapeutic target for severe RSV infection.