respiratory syncytial virus respiratory syncytial virus respiratory syncytial virus (rsv), also called human respiratory syncytial virus (hrsv) and human orthopneumovirus, is a common, contagious virus that causes infections of the respiratory tract. it is a negative-sense, single-stranded rna virus. its name is derived from the large cells known as syncytia that form when infected cells fuse. human orthopneumovirus electron micrograph of rsv virus classification (unranked): virus realm: riboviria kingdom: orthornavirae phylum: negarnaviricota class: monjiviricetes order: mononegavirales family: pneumoviridae genus: orthopneumovirus species: human orthopneumovirus synonyms human respiratory syncytial virus (hrsv) respiratory syncytial virus (rsv) rsv is the single most common cause of respiratory hospitalization in infants, and reinfection remains common in later life: it is a notable pathogen in all age groups. infection rates are typically higher during the cold winter months, causing bronchiolitis in infants, common colds in adults, and more serious respiratory illnesses such as pneumonia in the elderly and immunocompromised. rsv can cause outbreaks both in the community and in hospital settings. following initial infection via the eyes or nose, the virus infects the epithelial cells of the upper and lower airway, causing inflammation, cell damage, and airway obstruction. a variety of methods are available for viral detection and diagnosis of rsv including antigen testing, molecular testing, and viral culture. the main prevention measures include hand-washing and avoiding close contact with infected individuals. in may 2023, the us food and drug administration (fda) approved the first rsv vaccine, arexvy (developed by gsk plc), for adults aged 60 and older. the prophylactic use of palivizumab or nirsevimab can prevent rsv infection in high-risk infants. treatment for severe illness is primarily supportive, including oxygen therapy and more advanced breathing support with cpap or nasal high flow oxygen, as required. in cases of severe respiratory failure, intubation and mechanical ventilation may be required. ribavirin is the only antiviral medication licensed for the treatment of rsv in children, although its use remains controversial. history rsv was first discovered in 1956 when researchers isolated a virus from a population of chimpanzees with respiratory illness. they named the virus cca (chimpanzee coryza agent). in 1957, this same virus was identified by robert m. chanock in children with respiratory illness. studies of human antibodies in infants and children revealed that the infection was common in early life. the virus was later renamed human orthopneumovirus, or human respiratory syncytial virus (hrsv). several other pneumoviruses exist that show great similarity to hrsv. most notable of these is bovine rsv (brsv), which shares approximately 80% of its genome with hrsv. it also shares hrsv's predilection for the young, causing more severe disease in calves less than 6 months old. because brsv-infected calves have an almost identical presentation to hrsv-infected children, this has proven to be an important animal model in rsv research. signs and symptoms rsv infection can present with a wide variety of signs and symptoms that range from mild upper respiratory tract infections (urti) to severe and potentially life-threatening lower respiratory tract infections (lrti) requiring hospitalization and mechanical ventilation. while rsv can cause respiratory tract infections in people of all ages and is among the most common childhood infections, its presentation often varies between age groups and immune status. reinfection is common throughout life, but infants and the elderly remain at highest risk for symptomatic infection. children most children will experience at least one rsv infection by age two. most childhood rsv infections are fairly self-limited with typical upper respiratory tract signs and symptoms, such as nasal congestion, runny nose, cough, and low-grade fever. inflammation of the nasal mucosa (rhinitis) and throat (pharyngitis), as well as redness of the eyes (conjunctival infection), may be seen on exam. approximately 15–50% of children will go on to develop more serious lower respiratory tracts infections, such as bronchiolitis, viral pneumonia, or croup. infants are at the highest risk of disease progression. bronchiolitis is a common lower respiratory tract infection characterized by inflammation and obstruction of the small airways in the lungs. while several viruses can cause bronchiolitis, rsv is responsible for about 70% of cases. it usually presents with 2 to 4 days of runny nose and congestion followed by worsening cough, noisy breathing, tachypnea (fast breathing), and wheezing. as infants work harder to breathe, they can also show signs of respiratory distress, such as subcostal retractions (when the belly pulls under the ribcage), intercostal retractions (when the muscles between the ribs pull inward), grunting, and nasal flaring. if the child has not been able to feed adequately, signs of dehydration may also be present. fever may be present, but high-grade fever is uncommon. crackles and wheezing can often be heard on auscultation, and oxygen saturation levels may be decreased. in very young infants under six weeks of age, and particularly in premature infants, signs of infection may be less specific. they may have minimal respiratory involvement. instead, they may exhibit decreased activity, irritability, poor feeding, or breathing with difficulties. this can also be accompanied by apneic spells, or brief pauses in breathing. adults reinfection with rsv remains common throughout life. reinfection in adulthood often produces only mild to moderate symptoms indistinguishable from the common cold or sinus infection. infection may also be asymptomatic. if present, symptoms are generally isolated to the upper respiratory tract: runny nose, sore throat, fever, and malaise. in the vast majority of cases, nasal congestion precedes the development of cough. in contrast to other upper respiratory infections, rsv is also more likely to cause new onset wheeze in adults. only about 25% of infected adults will progress to significant lower respiratory tract infection, such as bronchitis or tracheobronchitis. while rsv very rarely causes severe disease in healthy adults, it can cause morbidity and mortality in the elderly and in those with underlying immune compromise or cardiopulmonary disease. older adults have a similar presentation to younger adults but tend to have greater symptom severity with increased risk of lower respiratory tract involvement. in particular, the elderly are more likely to experience pneumonia, respiratory distress, and death. immunocompromised in both adults and children, those who are immunocompromised are at an increased risk of severe infection with rsv. infected individuals in this group are more likely to progress from upper to lower respiratory tract involvement and have prolonged viral shedding. symptom severity seems to be closely related to the extent of immune suppression. those who have undergone hematopoietic stem cell transplant (hsct), intensive chemotherapy, and lung transplant are particularly susceptible. bone marrow transplant patients appear to be at highest risk, especially prior to marrow engraftment. in this group, rsv infection carries a nearly 80% risk of both pneumonia and death. complications population complications of rsv infection children short term, hospitalized children are at risk of developing: atelectasis / pulmonary infiltrates acute otitis media lung hyperinflation respiratory failure apnea bacterial pneumonia long term, children are at risk of developing the following chronic conditions that may persist into adulthood: asthma & recurrent wheezing, particularly among those with severe rsv infection in early life allergy acute neurologic complications adults the following are more common in elderly adults or those with underlying immunocompromise or cardiopulmonary conditions: pneumonia respiratory distress acute exacerbation of underlying chronic illness (copd, asthma, congestive heart failure) permanent decline in lung function in patients with copd immunocompromised some immunocompromised groups are at higher risk of specific complications, such as: bone marrow transplant recipients → pneumonia, death lung transplant recipients → chronic graft dysfunction, acute pneumonitis, obliterative bronchiolitis cause risk factors risk factors for development of severe lower respiratory tract infection with rsv vary by population. population risk factors for progression to lower respiratory infection with rsv children prematurity low birth weight male sex having older siblings maternal smoking during pregnancy history of atopy (tendency to develop allergic diseases) no breastfeeding household crowding congenital heart or lung disease adults & elderly older age (>65 years of age) chronic heart or lung disease (especially copd) functional disability residence in a care home immunocompromised lymphopenia neutropenia graft-versus-host disease use of corticosteroids or myeloablative conditioning regimens recent hematopoietic stem cell transplant virology a phylogenetic tree of the pneumovirus & paramyxovirus families taxonomy rsv is a negative-sense, single-stranded rna virus. the scientific name for this viral species is human orthopneumovirus. this is synonymous with human respiratory syncytial virus (hrsv), which is often shortened to just rsv. it belongs to the genus orthopneumovirus, family pneumoviridae, order mononegavirales. its name comes from the fact that f proteins on the surface of the virus cause neighboring cell membranes to merge, creating large multinucleated syncytia. antigenic subtypes rsv is divided into two antigenic subtypes, a and b, based on the reactivity of the f and g surface proteins to monoclonal antibodies. the subtypes tend to circulate simultaneously within local epidemics, although subtype a tends to be more prevalent. generally, rsv subtype a (rsva) is thought to be more virulent than rsv subtype b (rsvb), with higher viral loads and faster transmission time. to date, 16 rsva and 22 rsvb clades have been identified. among rsva, the ga1, ga2, ga5, and ga7 clades predominate; ga7 is found only in the united states. among rsvb, the ba clade predominates worldwide. genome rsv structure and genome organization. (a) ~150 nm rsv virion particle and (b) single-stranded negative-sense rna genome consisting of 10 genes (ns1-ns2-n-p-m-sh-g-f-m2-l). rsv has a negative-sense, single-stranded rna genome. the genome is linear and approximately 15,000 nucleotides in length. it is non-segmented which means that, unlike influenza, rsv cannot participate in the type of genetic reassortment and antigenic shifts responsible for large pandemics. it has 10 genes encoding for 11 proteins. the gene order is ns1-ns2-n-p-m-sh-g-f-m2-l, with the ns1 and ns2 gene serving as nonstructural promoter genes. electron micrograph of rsv particle, which has variable shapes. structure and proteins filamentous rsv particles rsv is a medium-sized (~150 nm) enveloped virus. while most particles are spherical, filamentous species have also been identified. the genome rests within a helical nucleocapsid and is surrounded by matrix protein and an envelope containing viral glycoproteins. there are 11 proteins, described further in the table below. rsv proteins and their function and location in the virion location in the virion protein alternative name function additional information lipid envelope (transmembrane surface proteins) g glycoprotein viral attachment to ciliated cells of the host airway f and g glycoproteins are the two major surface proteins that control viral attachment and the initial stages of infection. f and g proteins are also the primary targets for neutralizing antibodies during natural infection. f fusion protein fusion of viral and host cell membranes; syncytium formation sh small hydrophobic protein viroporin; ion channel participates in cell fusion, but no known neutralizing epitope inner envelope face m matrix protein assembly ribonucleocapsid n nuceloprotein rna-binding involved in genome transcription, rna replication, and particle budding p phosphoprotein phosphorylation l "large" protein rna-dependent rna polymerase m2-1 - transcription processivity factor regulatory m2-2 - regulation of transcription / rna replication nonstructural ns-1 - involved in evasion of the innate immune system act by inhibiting apoptosis & inhibiting type i ifn signaling ns-2 - g protein false-color artistic rendering of rsv. g- glycoproteins are shown in light blue, with f-glycoproteins in orange surface protein g (glycoprotein) is primarily responsible for viral attachment to host cells. this protein is highly variable between strains. g protein exists in both membrane-bound and secreted forms. the membrane-found form is responsible for attachment by binding to glycosaminoglycans (gags), such as heparan sulfate, on the surface of host cells. the secreted form acts as a decoy, interacting with antigen presenting cells to inhibit antibody-mediated neutralization. g protein also contains a cx3c fractalkine-like motif that binds to the cx3c chemokine receptor 1 (cx3cr1) on the surface of ciliated bronchial host cells. this binding may alter cellular chemotaxis and reduce the migration of immune cells into the lungs of infected individuals. g protein also alters host immune response by inhibiting signaling from several toll-like receptors, including tlr4. f protein surface protein f (fusion protein) is responsible for fusion of viral and host cell membranes, as well as syncytium formation between viral particles. its sequence is highly conserved between strains. while viral attachment appears to involve both f and g proteins, f fusion occurs independently of g. f protein exists in multiple conformational forms. in the prefusion state (pref), the protein exists in a