Respiratory Syncytial Virus (RSV) is a highly prevalent pathogen responsible for respiratory tract infections worldwide, particularly affecting infants, young children, and older adults. It is the leading cause of lower respiratory tract disease, such as bronchiolitis and pneumonia, in infants globally. Understanding how RSV attacks the respiratory system and how the body responds is necessary for developing effective treatments and preventative measures.
Anatomy of the RSV Virion
The Respiratory Syncytial Virus is classified as an enveloped virus, holding a single-stranded, non-segmented, negative-sense RNA genome encased within a lipid membrane derived from the host cell. This genetic material requires the virus to carry its own machinery for replication once inside a host cell.
The viral envelope is studded with two major glycoproteins that dictate the start of the infection process: the Fusion (F) protein and the Attachment (G) protein. The G protein is primarily responsible for recognizing and binding to specific receptors on the host cell surface, initiating the infection. The F protein mediates the subsequent fusion of the viral envelope with the host cell membrane, which is essential for viral entry.
The genetic material, a ribonucleoprotein complex, is protected by the Nucleoprotein (N) and is associated with the viral polymerase complex. This complex consists of the Large (L) protein, the RNA-dependent RNA polymerase, and the Phosphoprotein (P). These proteins are necessary for transcribing the viral genes and replicating the genome.
Cellular Entry and Replication Cycle
The infection cycle begins when the G protein attaches to receptors on the apical surface of ciliated epithelial cells lining the respiratory tract. One known receptor is the CX3C chemokine receptor 1 (CX3CR1), which helps target the virus specifically to these airway cells. After this initial binding, the Fusion (F) protein undergoes a conformational change.
This change drives the merger of the viral lipid envelope with the host cell membrane, allowing the viral core to enter the cell’s cytoplasm. The viral polymerase complex begins its work within distinct sites known as inclusion bodies. The L protein first transcribes the negative-sense RNA genome into messenger RNA (mRNA), which is then translated by the host cell machinery into the various viral proteins.
The polymerase complex then switches to genome replication, synthesizing new negative-sense RNA genomes. New viral components, including surface proteins, are synthesized and transported to the cell membrane. The matrix (M) protein coordinates the final assembly, guiding the new nucleocapsids toward the cell membrane where they interact with the F and G proteins. The mature, newly formed virions then bud from the host cell membrane, acquiring their lipid envelope in the process and spreading the infection to neighboring cells.
Direct Pathological Effects on Airway Tissues
Viral replication causes direct damage to the ciliated epithelial cells lining the small airways, or bronchioles. The viral F protein mediates the fusion of infected cells with neighboring uninfected cells, forming large, multinucleated masses called syncytia.
The widespread infection leads to the necrosis and sloughing of these damaged epithelial cells into the airway lumen. This cellular debris, combined with excessive mucus and inflammation, creates plugs that physically obstruct the narrow bronchioles. The resulting small airway obstruction is a hallmark of severe RSV disease, particularly in infants whose airways are already small in diameter.
The physical obstruction prevents air from escaping the lung, leading to air trapping and hyperinflation of the distal lung tissue. The loss of the ciliated epithelium also impairs mucociliary clearance, meaning the thick mucus and debris are not effectively removed, further worsening the obstruction. This localized damage causes the wheezing, coughing, and labored breathing that characterize a severe RSV infection.
Host Immune Response and Immunopathology
The body’s initial defense against RSV involves the innate immune system, recruiting cells like macrophages and neutrophils to the site of infection. Respiratory epithelial cells and other local immune cells release chemokines and cytokines, such as interleukin-8 (IL-8), to attract these inflammatory cells. This initial response attempts to control the virus but also contributes to inflammatory swelling and edema in the airway walls.
The adaptive immune response follows, involving T-cells and B-cells. CD4+ T-cells coordinate the response, helping B-cells produce antibodies and promoting the activity of CD8+ T-cells. These cytotoxic CD8+ T-cells kill infected cells and clear the virus, while neutralizing antibodies target the F and G proteins to prevent new infections.
However, the immune response itself is a major factor in the severity of RSV disease, a concept known as immunopathology. An overly vigorous or poorly regulated T-cell response leads to excessive inflammation, which exacerbates airway narrowing and edema. In infants, the combination of small airways and a disproportionately strong inflammatory reaction can make symptoms worse rather than better. This intense cellular infiltration and resulting edema contribute significantly to the airway obstruction observed in severe bronchiolitis.