Biology of human respiratory syncytial virus: Current perspectives in immune response and mechanisms against the virus

Abstract

Human respiratory syncytial virus (hRSV) remains a leading cause of morbidity and mortality in infants, young children, and older adults. hRSV infection's limited treatment and vaccine options significantly increase bronchiolitis' morbidity rates. The severity and outcome of viral infection hinge on the innate immune response. Developing vaccines and identifying therapeutic interventions suitable for young children, older adults, and pregnant women relies on comprehending the molecular mechanisms of viral PAMP recognition, genetic factors of the inflammatory response, and antiviral defense. This review covers fundamental elements of hRSV biology, diagnosis, pathogenesis, and the immune response, highlighting prospective options for vaccine development.

Keywords: Current vaccines against hRSV; Immune response; Pathogenesis; Viral diagnosis; hRSV.

Fig. 1

Key targets in the RSV replication cycle. A. The RSV carries an RNA genome. 10 genes in the RSV genome encode for 11 proteins, with the M2 gene encoding for both M2–1 and M2–2 proteins. B. The respiratory syncytial virus (RSV) virion. The virion's filamentous structure is displayed. The M2–1 protein interacts directly with both the M and N proteins, while the large polymerase subunit (L) and phosphoprotein polymerase cofactor (P) bind to the N protein. The nucleocapsid, which consists of the RNA genome encased in N protein, is formed alongside the viral membrane, where attachment (G) and fusion (F) glycoproteins, small hydrophobic (SH) proteins, and the matrix (M) protein are embedded. C. RSV replication cycle and drug targets. The G protein initiates attachment by binding to cell surface factors, and the F protein aids in the nucleocapsid's entry into the cytoplasm. The F protein triggers viral and host membrane fusion by undergoing a significant conformational shift. In the inclusion body, the RSV polymerase complex, comprised of L and P proteins, produces both mRNAs and progeny genomes using the N-RNA complex as a template, with M2–1 assisting in transcription. The ER and Golgi apparatus synthesize, mature, and transport structural proteins. N protein plays a role in both the packaging of genomic RNA and the assembly of viral structures. Virus particles protrude from the cell membrane during the budding process. The process of fusion and replication is the primary target for inhibitor intervention. Reprinted with permission from (Zou et al., 2023). Copyright (2023) Elsevier B.V.

Fig. 2

The local human immune response to hRSV involves the production of type I interferons, recruitment of neutrophils, and production of antibodies. These cells, including neutrophils, dendritic cells, macrophages, and eosinophils, are the primary ones affected by hRSV infection. The response of cytokines, chemokines, and other immune molecules to local immune production is determined by their location and modulation in the infection process. During infection, the activated PRRs (TLR2, 3, 4, 7, and 9) are featured at the innate immune level. Reproduced with permission from Frontiers Publishing Partnership (Creative Commons Attribution 4.0 International License) (Correa et al., 2023).