Background
Respiratory syncytial virus (RSV), a common pathogen of lower respiratory tract infections in children, is the leading causative agent of hospitalization in infants worldwide. RSV can also cause serious health problems in the elderly and immunocompromised populations. RSV infections have a seasonal trend, usually starting in the fall and winter and ending in the spring and summer, with an epidemic period lasting about 5-6 months. RSV mainly causes acute lower respiratory tract infections, which are most commonly seen clinically as capillary bronchitis or pneumonia. Symptoms are characterized by wheezing and coughing, and severe patients may present with shortness of breath and intercostal space depression.
RSV belongs to the family Pneumoviridae, genus Orthopneumovirus, and is a non-segmented single-stranded negative-stranded RNA virus. There is only one serotype of RSV, which is divided into subtypes A and B2. The total length of the virus genome is 15.2kb, containing 10 genes encoding 11 proteins, including two non-structural proteins (NS1, NS2) and nine structural proteins (N, P, M, L, M2-1, M2-2, G, F, SH). NS1 and NS2 can inhibit interferon production and participate in immune escape. Adhesion protein G, fusion protein F and small hydrophobic protein SH are membrane proteins.
Figure 1. Structure of RSV
(Source: Azzari C, et al. 2021)
The F protein is an important antigen of RSV and is involved in mediating fusion of the virus with the host cell membrane. It induces the body to produce neutralizing antibodies. Due to the complexity of RSV, RSV vaccine research progress has been slow. The first generation of RSV vaccine, a fully inactivated vaccine, did not produce a protective response in infants and young children, but instead produced enhanced respiratory disease in vaccinated children during their initial infection, which ultimately led to the deaths of two infants. Another obstacle to RSV vaccine development is limited understanding of the immune response after RSV infection. Human infection with RSV can form humoral and cellular immunity, but the immunity is not durable, the protection is unstable, may cause RSV repeated infection. The F protein has been a major target protein in the development of RSV vaccines in recent years. When the protein plays the role of mediating viral membrane fusion, its conformation changes from Pre-F to Post-F. Due to the unstable structure of Pre-F, researchers tend to choose Post-F as the main conformation of F protein in vaccine development, but this also leads to the lack of vaccine effectiveness. With the in-depth research and technological development, a stable Pre-F form of RSV vaccine has been developed and is currently in the clinical trial stage.
Alternative Names
Respiratory syncytial virus Fusion protein
Respiratory syncytial virus F
References
- 1. Gatt D, et al. Prevention and Treatment Strategies for Respiratory Syncytial Virus (RSV). Pathogens. 2023 Jan 17;12(2):154.
- 2. Azzari C, et al. Epidemiology and prevention of respiratory syncytial virus infections in children in Italy. Ital J Pediatr. 2021 Oct 2;47(1):198.