Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies

Abstract

Respiratory syncytial virus (RSV) is one of the most important viral pathogens causing respiratory tract infection in infants, the elderly and people with poor immune function, which causes a huge disease burden worldwide every year. It has been more than 60 years since RSV was discovered, and the palivizumab monoclonal antibody, the only approved specific treatment, is limited to use for passive immunoprophylaxis in high-risk infants; no other intervention has been approved to date. However, in the past decade, substantial progress has been made in characterizing the structure and function of RSV components, their interactions with host surface molecules, and the host innate and adaptive immune response to infection. In addition, basic and important findings have also piqued widespread interest among researchers and pharmaceutical companies searching for effective interventions for RSV infection. A large number of promising monoclonal antibodies and inhibitors have been screened, and new vaccine candidates have been designed for clinical evaluation. In this review, we first briefly introduce the structural composition, host cell surface receptors and life cycle of RSV virions. Then, we discuss the latest findings related to the pathogenesis of RSV. We also focus on the latest clinical progress in the prevention and treatment of RSV infection through the development of monoclonal antibodies, vaccines and small-molecule inhibitors. Finally, we look forward to the prospects and challenges of future RSV research and clinical intervention.

Keywords: Antibody; Infection; Intervention; Pathogenesis; Respiratory syncytial virus; Vaccine.

Figure 1

Timeline of RSV discovery and important related events.

Figure 2

Schematic diagram of the RSV virion and its genome structure. (a) The general structure of the RSV virion and its encoded proteins. (b) The genome organization of RSV consists of 11 open reading frames (ORFs), including 2 ORFs adjacent to the 3′ leader region that encode nonstructural proteins related to evading the innate immune response, and ORFs that encode structural proteins: nucleoprotein (N), phosphoprotein (P), matrix protein (M), small hydrophobic (SH) protein, glycoprotein (G), fusion protein (F), M2 protein, and polymerase (L) protein.

Figure 3

Potential receptors of RSV binding for virus entry into host cells. Potential receptors, such as annexin II, HSPG/GAG and CX3CR1, bind to the RSV G glycoprotein, and TLR4, ICAM-1, EGFR, NCL and IGF1R bind to the RSV F glycoprotein, tether RSV virions to the cell surface.

Figure 4

Schematic of the RSV life cycle. RSV first enters the host cell via macropinocytosis or cell-surface fusion by binding to the host cell receptor. The virus fuses with the cell membrane and releases the RNP complex to initiate replication and transcription in an inclusion body to produce the genomes, internal component proteins, and surface proteins required by the virus. Genomes are assembled to form new RNP complexes, and proteins are translated on the endoplasmic reticulum and then moved to the Golgi apparatus where they mature. Finally, the RNP complexes are transferred to the plasma membrane to germinate new filamentous RSV virions, completing the viral life cycle.