Innate Immune Evasion by Human Respiratory Syncytial Virus

Abstract

Respiratory syncytial virus (RSV) is the leading cause of severe respiratory infection in young children. Nearly all individuals become infected in their early childhood, and reinfections with RSV are common throughout life. Primary infection with RSV is usually involved in the symptom of bronchiolitis and pneumonia in the lower respiratory tract, which accounts for over 3 million hospitalizations and approximately 66,000 deaths annually worldwide. Despite the widespread prevalence and high morbidity and lethality rates of diseases caused by RSV infection, there is currently no licensed RSV vaccine. During RSV infection, innate immunity plays the first line of defense to suppress RSV infection and replication. However, RSV has evolved multiple mechanisms to evade the host’s innate immune responses to gain a window of opportunity for efficient viral replication. This review discusses the comprehensive interaction between RSV infection and the host antiviral innate immunity and updates recent findings on how RSV modulates the host innate immune response for survival, which may provide novel insights to find potent drug targets and vaccines against RSV.

Reshaping Our Knowledge: Advancements in Understanding the Immune Response to Human Respiratory Syncytial Virus

“…Deletion of the SH protein in RSV induces viral attenuation. Furthermore, the role of the SH protein in the anti-apoptotic process in infected cells was recently found [ 2 , 25 , 26 , 27 , 28 ].…”

RSV Replication, Transmission, and Disease Are Influenced by the RSV G Protein

“…The F protein is a major target for antiviral drug and vaccine development, and both the G and F proteins are the antigens targeted by neutralizing antibodies induced by infection. The G protein is produced either as a membrane-bound or secreted protein (e.g., soluble G) that mediates immune evasion [8,9]. The F protein is a trimer in the infected cell membrane in its prefusion form but refolds into a post-fusion form.…”

DUOX2 regulates secreted factors in virus‐infected respiratory epithelial cells that contribute to neutrophil attraction and activation

“…Specifically, they are known to antagonize the antiviral IFN response, while inducing an exaggerated proinflammatory response often characterized by an accumulation of neutrophils in the airway tract. 7 , 8 , 9 Therefore, the understanding of the innate responses of infected ECs and how they mediate leukocytes recruitment to the airway mucosa is key.…”

“…The capacity of respiratory RNA viruses to modulate the rate, magnitude, and quality of antiviral and proinflammatory responses is associated with the severity of the pathogenesis. Specifically, they are known to antagonize the antiviral IFN response, while inducing an exaggerated proinflammatory response often characterized by an accumulation of neutrophils in the airway tract 7–9 . Therefore, the understanding of the innate responses of infected ECs and how they mediate leukocytes recruitment to the airway mucosa is key.…”