Immunity Cell Responses to RSV and the Role of Antiviral Inhibitors: A Systematic Review

Antigen-presenting cells recognize respiratory syncytial virus antigens, and produce cytokines and chemokines that act on immune cells. Dendritic cells play the main role in inflammatory cytokine responses. Similarly, alveolar macrophages produce IFN-beta, IFN-alpha, TNF-alpha, IL-6, CXCL10, and CCL3, while alternatively activated macrophages differentiate at the late phase, and require IL-13 or IL-4 cytokines. Furthermore, activated NKT cells secrete IL-13 and IL-4 that cause lung epithelial, endothelial and fibroblasts to secrete eotaxin that enhances the recruitment of eosinophil to the lung. CD8+ and CD4+T cells infection by the virus decreases the IFN-gamma and IL-2 production. Despite this, both are involved in terminating virus replication. CD8+T cells produce a larger amount of IFN-gamma than CD4+T cells, and CD8+T cells activated under type 2 conditions produce IL-4, down regulating CD8 expression, granzyme and IFN-gamma production. Antiviral inhibitors inhibit biological functions of viral proteins. Some of them directly target the virus replication machinery and are effective at later stages of infection; while others inhibit F protein dependent fusion and syncytium formation. TMC353121 reduces inflammatory cytokines, TNF-alpha, IL-6, and IL-1 beta and chemokines, KC, IP-10, MCP and MIP1-alpha. EDP-938 inhibits viral nucleoprotein (N), while GRP-156784 blocks the activity of respiratory syncytial virus ribonucleic acid (RNA) polymerase. PC786 inhibits non-structural protein 1 (NS-1) gene, RANTES transcripts, virus-induced CCL5, IL-6, and mucin increase. In general, it is an immune reaction that is blamed for the disease severity and pathogenesis in respiratory syncytial virus infection. Anti-viral inhibitors not only inhibit viral entry and replication, but also may reduce inflammatory cytokines and chemokines. Many respiratory syncytial virus inhibitors are proposed; however, only palivizumab and ribavirin are approved for prophylaxis and treatment, respectively. Hence, this review is focused on immunity cell responses to respiratory syncytial virus and the role of antiviral inhibitors.

Automated summary

Antigen-presenting cells and immune cells play important roles in respiratory syncytial virus infection, producing cytokines and chemokines that affect disease severity and pathogenesis.