Respiratory syncytial virus (RSV) is a ubiquitous pathogen. Respiratory syncytial virus infection can manifest with a variety of clinical symptoms, including upper respiratory tract infections (URTIs), bronchiolitis, pneumonia, exacerbations of asthma, and viral-induced wheeze. Human respiratory syncytial virus (HRSV, RSV for short) was first isolated from chimpanzees in 1956 and subsequently discovered in infants with severe lower respiratory tract disease. It is a non-segmental negative-sense single-stranded enveloped RNA virus belonging to the family of Paramyxoviridae, genus Pneumovirus, subfamily Pneumovirinae. Its 10 genes encode 11 proteins, as two overlapping open reading frames in the M2 mRNA yield two distinct matrix proteins, M2-1 and M2-2. The viral envelope contains three proteins, the G glycoprotein, the fusion (F) glycoprotein, and the small hydrophobic (SH) protein. RSV consists of five additional structural proteins, namely large (L) protein, nucleocapsid (N), phosphoprotein (P), matrix (M) and M2-1, and two nonstructural proteins (NS1 and NS2).
The respiratory syncytial virus is a biosafety level 2 organism. Serological testing is not widely used for the diagnosis of the respiratory syncytial virus. In patients, 5 years of age and older, acute and convalescent-phase serological testing combined with PCR improved the diagnostic yield of RSV from 8.3% with PCR alone to 11.3%. Enzyme immunoassay (EIA) for envelope glycoproteins is more sensitive than HEp-2 tube culture. However, the time required for serological response assay and comparison between paired and convalescent-phase serum samples is not useful for guiding patient care. Virus neutralization is also used to quantify the protective capacity of RSV antibodies in human serum.
Figure 1. RSV replication cycle.
The infection cycle begins when RSVs bind to receptors on the cell surface and fuses their envelope with the plasma membrane (Figure 1). This process transports the viral nucleocapsid into the cytoplasm. The nucleocapsid is composed of viral genomic RNA, wrapped with nucleoprotein (N) along its length to form a helical structure, and associated with viral RNA-dependent polymerase which is a complex comprising the viral large polymerase subunit (L), phosphoprotein (P), and transcription factor, M2-1. Once the nucleocapsid enters the cytoplasm, the polymerase transcribes the viral mRNAs and replicates the genome by a positive-sense RNA intermediate, the antigenome, which serves as a template for further genomic RNA synthesis. The newly synthesized genome (and antigenome) is encapsulated by the N protein upon synthesis and binds to the polymerase protein to form the nucleocapsid. Nucleocapsids are transported to the plasma membrane, where they bind to other viral structural proteins, and virions are released by budding.
Currently, treatment of RSV disease is mainly supportive. Ribavirin is the only licensed antiviral therapy for RSV disease. However, its use is currently limited to life-threatening RSV infections in immunocompromised patients. Currently, there is no vaccine to prevent respiratory syncytial virus infection. There is an unmet need for clinically effective, safe, and cost-effective preventive and therapeutic options, including antiviral treatments, vaccines, and half-life-extending mAbs. Creative Diagnostics supports clients in respiratory syncytial virus antiviral research and development with extensive knowledge to characterize antiviral agents.
For additional information about Respiratory Syncytial Virus (RSV) Antiviral Services, please contact us.