Clinical meaning
Respiratory syncytial virus (RSV) is an enveloped, single-stranded, negative-sense RNA virus of the family Pneumoviridae. The viral envelope contains two critical surface glycoproteins: the G protein (attachment protein) that binds to cell surface receptors (CX3CR1 on ciliated epithelial cells) mediating initial viral attachment, and the F protein (fusion protein) that facilitates fusion of the viral envelope with the host cell membrane, allowing viral RNA to enter the cytoplasm. Once inside the cell, the RSV RNA-dependent RNA polymerase (carried within the virion) transcribes the negative-sense RNA genome into positive-sense mRNA, which is then translated by host ribosomes into viral proteins. New viral RNA is replicated, assembled with structural proteins at the cell membrane, and released by budding — each infected cell produces thousands of new virions over a 20-24 hour replication cycle before the host cell undergoes necrosis and lyses. The innate immune response to RSV in infants is characterized by a Th2-predominant cytokine profile (IL-4, IL-5, IL-13) rather than the protective Th1 response (IFN-gamma, IL-12) seen in older children and adults. This Th2 skewing occurs because the infant immune system is inherently biased toward Th2 responses (protective against extracellular parasites but less effective against intracellular pathogens), and RSV actively suppresses Th1 responses through its nonstructural proteins NS1 and NS2, which inhibit type I interferon signaling. The Th2 predominance promotes IgE-mediated mast cell degranulation and eosinophilic inflammation in the airways, contributing to bronchospasm, mucus hypersecretion, and airway hyperreactivity — this may explain the epidemiological association between severe RSV bronchiolitis in infancy and subsequent development of recurrent wheezing/asthma. The bronchiolar obstruction mechanism involves three concurrent processes: (1) epithelial sloughing — necrotic epithelial cells detach from the basement membrane and accumulate in the airway lumen as cellular debris; (2) inflammatory exudate — neutrophils, macrophages, lymphocytes, and fibrin form a proteinaceous matrix within the lumen; (3) mucus hypersecretion — goblet cell hyperplasia and submucosal gland stimulation produce excessive viscid mucus. These three components combine to form intraluminal plugs that cause partial or complete bronchiolar obstruction. The pathophysiological consequences of bronchiolar obstruction include: air trapping (ball-valve mechanism where air enters during inspiration but cannot exit during expiration due to dynamic airway compression), pulmonary hyperinflation (visible on CXR as flattened diaphragms, increased AP diameter, and widened intercostal spaces), atelectasis (complete obstruction leads to distal air absorption and alveolar collapse), and V/Q mismatch (perfused but poorly ventilated lung units create intrapulmonary shunting). Infants are particularly vulnerable to bronchiolitis for several anatomical and physiological reasons: (1) small airway caliber — infant bronchioles are approximately 1 mm in diameter, so even 1 mm of mucosal edema reduces the cross-sectional area by 75% and increases resistance 16-fold per Poiseuille's law; (2) obligate nose breathing — infants under 4-6 months preferentially breathe through the nose, so nasal congestion from RSV causes significant respiratory compromise; (3) immature immune system — limited IgA secretion, Th2-skewed responses, and absence of RSV-specific memory T cells; (4) lack of collateral ventilation — the pores of Kohn (interalveolar) and channels of Lambert (bronchioloalveolar) are not fully developed until approximately 3-4 years of age, meaning obstructed alveoli cannot be ventilated through alternative pathways, making atelectasis more likely; (5) compliant chest wall — the highly compliant infant rib cage is easily deformed by negative intrathoracic pressure, contributing to chest wall retractions rather than effective air movement; (6) fewer type II pneumocytes — reduced surfactant production contributes to alveolar instability and collapse.