Human Respiratory Syncytial Virus: Infection and Pathology

Abstract

The human respiratory syncytial virus (hRSV) is by far the major cause of acute lower respiratory tract infections (ALRTIs) worldwide in infants and children younger than 2 years. The overwhelming number of hospitalizations due to hRSV-induced ALRTI each year is due, at least in part, to the lack of licensed vaccines against this virus. Thus, hRSV infection is considered a major public health problem and economic burden in most countries. The lung pathology developed in hRSV-infected individuals is characterized by an exacerbated proinflammatory and unbalanced Th2-type immune response. In addition to the adverse effects in airway tissues, hRSV infection can also cause neurologic manifestations in the host, such as seizures and encephalopathy. Although the origins of these extrapulmonary symptoms remain unclear, studies with patients suffering from neurological alterations suggest an involvement of the inflammatory response against hRSV. Furthermore, hRSV has evolved numerous mechanisms to modulate and evade the immune response in the host. Several studies have focused on elucidating the interactions between hRSV virulence factors and the host immune system, to rationally design new vaccines and therapies against this virus. Here, we discuss about the infection, pathology, and immune response triggered by hRSV in the host.

Fig. 1

hRSV virion and genome structure. (A) Schematic representation of hRSV virion particle. In the rectangle, each protein are represented with their principal associated function. (B) Schematic representation of hRSV genome. Transcription is mediated by L protein which generates 11 viral mRNAs, with cap (vertical bars at the beginning) and polyA (horizontal bars at the ends). One mRNA for each proteins and width of each box represent the quantity of transcription rate of each gene. Replication is mediated by L protein and is necessary for the generation of antigenome product to generate new hRSV RNA. TrC segment in the 3′ is where replication promotor is located.

Fig. 2

hRSV infection of airway epithelial cells: (1) G and F proteins interact with host receptors to initiate virus entry. (2) RNP complex is release, by the separation of RNP with M protein. (3) Replication of viral RNA. (4) Transcription and translation of viral proteins. (5) M protein is imported to the nucleus and inhibit host cells transcription. (6) M protein is exported to the nucleus and is transported to cholesterol-rich domains. (7) M protein starts to interact with surface proteins as beginning of assembly. (8) RNP interacts with M protein to finish the assembly process. (9) Budding of nascent virions.

Fig. 3

Immune response trigged by hRSV infection in respiratory airways. hRSV reaches the lower respiratory tract and is recognized for respiratory epithelial cells by pattern recognition receptors (PRRs) expressed leading to the secretion of innate cytokines and chemokines such as TSLP, IL-13, and IL-25. Inflammatory cytokines and chemokines promote the recruitment of innate immune cells into the lungs, such as eosinophils, neutrophils, and monocytes. The inflammatory environment induced by the innate immune cell recruitment and mucus production together with an excessive Th2 and Th17 response generate destruction of the respiratory epithelium and the obstruction of distal bronchiolar airways.

Fig. 4

hRSV blocks the DC-T-cell synapse assembly. hRSV elicits immune host system by impairment T-cell activation. The DC-T-cell synapse assembly is interfered by decreasing Golgi polarization, altering the cytokines secreted in the environment, reducing the surface cognate peptide MHC and impairing the TCR engagement.

Fig. 5

Model for hRSV spread from the lungs to the CNS. The figure shows the possible hRSV spread from the lungs to CNS through the hematogenous pathway.