Infection with human respiratory syncytial virus (hRSV) is transmitted through close contact, fomites, and aerosolized droplets. RSV first infects the epithelial lining of the upper respiratory tract and nasopharynx where the virus begins to replicate, and from there it may spread to the lower respiratory tract - bronchioles and alveoli - especially in infants. Immune response to RSV infection increases mucus production which, in combination with inflammation, leads to the narrowing of airways and bronchiolitis. Experimental vaccination with a formalin-inactivated RSV has been associated with vaccine-enhanced disease, which has hindered vaccine development and led to advancement of costly and modestly effective therapies based on monoclonal antibodies (mAb) and small molecules, which act to block RSV entry and have been reserved for high-risk patients (reviewed in Battles and McLellan 2019, and Pandya et al. 2019). Recently, a prophylactic mAb Nirsevimab was approved for use in all infants (reviewed in Keam 2023). Some of the preF vaccines, which elicit immune response against the pre-fusion conformation of the F protein (pre-F), are in the late stages of clinical trial or undergoing approval for being used in elderly patients and pregnant women (reviewed in Jenkins et al. 2023).

RSV is classified into two distinct subtypes, RSV A and RSV B, predominantly based on antigenic and sequence-based variations in the viral envelope protein G, involved in virus attachment to the host cells. Multiple RSV genotypes are often in co-circulation with a dominance shift between RSV A and RSV B subtypes occurring every 1-2 years. The majority of RSV molecular studies use a limited number of historical isolates, the so-called laboratory strains, of which hRSV A substrain A2 is the most commonly used. If not indicated otherwise, the events described in this pathway refer to findings from hRSV A2-based studies.

For review, please refer to Battles and McLellan 2019, and Pandya et al. 2019.