Human respiratory syncytial virus
Human respiratory syncytial virus (RSV) is a virus that causes respiratory tract infections. It is a major cause of lower respiratory tract infections and hospital visits during infancy and childhood. A prophylactic medication (not a vaccine) exists for preterm (under 35 weeks gestation) infants, infants with certain congenital heart defects (CHD) or bronchopulmonary dysplasia (BPD), and infants with congenital malformations of the airway. Treatment is limited to supportive care (e.g. C-PAP), including oxygen therapy.
In the United States, 60% of infants are infected during their first RSV season, and nearly all children will have been infected with the virus by 2–3 years of age. Of those infected with RSV, 2–3% will develop bronchiolitis, necessitating hospitalization. Natural infection with RSV induces protective immunity which wanes over time—possibly more so than other respiratory viral infections—and thus people can be infected multiple times. Sometimes an infant can become symptomatically infected more than once, even within a single RSV season. Severe RSV infections have increasingly been found among elderly patients. Young adults can be re-infected every five to seven years, with symptoms looking like a sinus infection or a cold (infections can also be asymptomatic).
RSV is a negative-sense, single-stranded RNA virus of the family Paramyxoviridae, which includes common respiratory viruses such as those causing measles and mumps. RSV is a member of the paramyxovirus subfamily Pneumovirinae. Its name comes from the fact that F proteins on the surface of the virus cause the cell membranes on nearby cells to merge, forming syncytia.
Signs and symptoms
|Human respiratory syncytial |
An x ray of a child with RSV showing the typical bilateral perihilar fullness
|Classification and external resources|
|NCI||Human respiratory syncytial virus|
|Patient UK||Human respiratory syncytial virus|
The incubation time (from infection until symptoms arrive) is 4–5 days. For adults, RSV produces mainly mild symptoms, often indistinguishable from common colds and minor illnesses. The Centers for Disease Control consider RSV to be the "most common cause of bronchiolitis (inflammation of the small airways in the lung) and pneumonia in children under 1 year of age in the United States". For some children, RSV can cause bronchiolitis, leading to severe respiratory illness requiring hospitalization and, rarely, causing death. This is more likely to occur in patients that are immunocompromised or infants born prematurely. Other RSV symptoms common among infants include listlessness, poor or diminished appetite, and a possible fever.[unreliable medical source?]
Recurrent wheezing and asthma are more common among individuals who suffered severe RSV infection during the first few months of life than among controls; whether RSV infection sets up a process that leads to recurrent wheezing or whether those already predisposed to asthma are more likely to become severely ill with RSV has yet to be determined.
Symptoms of pneumonia in immuno-compromised patients such as in transplant patients and especially bone marrow transplant patients should be evaluated to rule out RSV infection. This can be done by means of PCR testing for RSV nucleic acids in peripheral blood samples if all other infectious processes have been ruled out or if it is highly suspicious for RSV such as a recent exposure to a known source of RSV infection.
The genome is ~15,000 nucleotides in length and is composed of a single strand of RNA with negative polarity. It has 10 genes encoding 11 proteins—there are 2 open reading frames of M2. The genome is transcribed sequentially from NS1 to L with reduction in expression levels along its length.
NS1 and NS2 inhibit type I interferon activity.
N encodes nucleocapsid protein that associates with the genomic RNA forming the nucleocapsid.
M encodes the Matrix protein required for viral assembly.
SH, G and F form the viral coat. The G protein is a surface protein that is heavily glycosylated. It functions as the attachment protein. The F protein is another important surface protein; F mediates fusion, allowing entry of the virus into the cell cytoplasm and also allowing the formation of syncytia. The F protein is homologous in both subtypes of RSV; antibodies directed at the F protein are neutralizing. In contrast, the G protein differs considerably between the two subtypes.
Nucleolin at the cell surface is the receptor for the RSV fusion protein. Interference with the nucleolin - RSV fusion protein interaction has been shown to be therapeutic against RSV infection in cell cultures and animal models.
L encodes the RNA polymerase.
The phosphoprotein P is a cofactor for the L protein.
Bayesian estimates of the mutation rates in the subtype A genomes give a mutation rate of 6.47×10−4 (credible interval: 5.56×10−4 – 7.38×10−4) substitutions/site/year. This is similar to other RNA viruses. The population size has remained constant over the last 70 years and the G protein appears to be the main site of diversifying selection. The most recent common ancestor evolved ~1943 (credible interval: 1923–1954).
RSV spreads easily by direct contact, and can remain viable for a half an hour or more on hands or for up to 5 hours on countertops.[dead link] Childcare facilities allow for rapid child-to-child transmission in a short period of time.
As the virus is ubiquitous in all parts of the world, avoidance of infection is not possible. A vaccine trial in 1960s using a formalin-inactivated vaccine (FI-RSV), increased disease severity in children who had been vaccinated. There is much active investigation into the development of a new vaccine, but at present no vaccine exists. Some of the most promising candidates are based on temperature sensitive mutants which have targeted genetic mutations to reduce virulence.
However, palivizumab (brand name Synagis manufactured by MedImmune), a moderately effective prophylactic drug is available for infants at high risk. Palivizumab is a monoclonal antibody directed against RSV surface fusion protein. It is given by monthly injections, which are begun just prior to the RSV season and are usually continued for five months. RSV prophylaxis is indicated for infants that are premature or have either cardiac or lung disease, but the cost of prevention limits use in many parts of the world. An antiviral drug—Ribavirin—is licensed for use, but its efficacy is limited.
Scientists are attempting to develop a recombinant Human respiratory syncytial virus vaccine that is suitable for intranasal instillation. Tests for determining the safety and level of resistance that can be achieved by the vaccine are being conducted in the chimpanzee, which is the only known animal that develops a respiratory illness similar to humans.
- Vaccine News Daily article "NOVAVAX Novavax, Inc. reports positive RSV vaccine Phase II clinical trial results" published Apr 2, 2013
RSV infection can be confirmed using Direct Fluorescent Antibody detection (DFA), Chromatographic rapid antigen detection or detection of viral RNA using RT PCR (Reverse transcription polymerase chain reaction). Quantification of viral load can be determined by Plaque Assay, antigen capture enzyme immunoassay (EIA), ELISA and HA, and quantification of antibody levels by HAI and Neutralisation assay.
Studies of nebulized hypertonic saline have shown that the "use of nebulized 3% HS is a safe, inexpensive, and effective treatment for infants hospitalized with moderately severe viral bronchiolitis" where "respiratory syncytial virus (RSV) accounts for the majority of viral bronchiolitis cases". One study noted a 26% reduction in length of stay: 2.6 ± 1.9 days, compared with 3.5 ± 2.9 days in the normal-saline treated group (p=0.05).
Supportive care includes fluids and oxygen until the illness runs its course. Salbutamol may be used in an attempt to relieve any bronchospasm if present. Increased airflow, humidified and delivered via nasal cannula, may be supplied in order to reduce the effort required for respiration. Adrenaline, bronchodilators, steroids, antibiotics, and ribavirin confer "no real benefit".
The RSV is virtually the same as chimpanzee coryza virus and can be transmitted from apes to humans, although transmission from humans to apes is more common.
- Glezen, WP; Taber, LH; Frank, AL; Kasel, JA (1986). "Risk of primary infection and reinfection with respiratory syncytial virus". American journal of diseases of children (1960) 140 (6): 543–6. PMID 3706232. doi:10.1001/archpedi.1986.02140200053026.
- Hall, Caroline Breese; Weinberg, Geoffrey A.; Iwane, Marika K.; Blumkin, Aaron K.; Edwards, Kathryn M.; Staat, Mary A.; Auinger, Peggy; Griffin, Marie R.; Poehling, Katherine A.; Erdman, Dean; Grijalva, Carlos G.; Zhu, Yuwei; Szilagyi, Peter (2009). "The Burden of Respiratory Syncytial Virus Infection in Young Children". New England Journal of Medicine 360 (6): 588–98. PMID 19196675. doi:10.1056/NEJMoa0804877.
- "Respiratory Syncytial Virus". CDC, Respiratory and Enteric Viruses Branch. October 17, 2008. Retrieved 2009-02-10.
- "RSV in Infants—LoveToKnow Baby". baby.lovetoknow.com. Retrieved 2010-01-26.
- Wu, P.; Dupont, W. D.; Griffin, M. R.; Carroll, K. N.; Mitchel, E. F.; Gebretsadik, T.; Hartert, T. V. (2008). "Evidence of a Causal Role of Winter Virus Infection during Infancy in Early Childhood Asthma". American Journal of Respiratory and Critical Care Medicine 178 (11): 1123–9. PMC 2588491. PMID 18776151. doi:10.1164/rccm.200804-579OC.
- "Examining His Own Body, Stanford Geneticist Stops Diabetes in Its Tracks". AAAS, sciencemag.org. 16 March 2012. Retrieved 2012-03-17.
- Chen, R.; Mias, G. I.; Li-Pook-Than, J.; Jiang, L.; Lam, H. Y. K.; Chen, R.; Miriami, E.; Karczewski, K. J.; Hariharan, M.; Dewey, F. E.; Cheng, Y.; Clark, M. J.; Im, H.; Habegger, L.; Balasubramanian, S.; O'Huallachain, M.; Dudley, J. T.; Hillenmeyer, S.; Haraksingh, R.; Sharon, D.; Euskirchen, G.; Lacroute, P.; Bettinger, K.; Boyle, A. P.; Kasowski, M.; Grubert, F.; Seki, S.; Garcia, M.; Whirl-Carrillo, M.; Gallardo, M. (2012). "Personal Omics Profiling Reveals Dynamic Molecular and Medical Phenotypes". Cell 148 (6): 1293–1307. PMC 3341616. PMID 22424236. doi:10.1016/j.cell.2012.02.009.
- Tayyari F, Marchant D, Moraes TJ, Duan W, Mastrangelo P, Hegele RG (August 14, 2011). "Identification of nucleolin as a cellular receptor for human respiratory syncytial virus". Nat Med 17 (9): 1132–5. PMID 21841784. doi:10.1038/nm.2444.
- Mastrangelo P, Hegele RG (November 2012). "The RSV fusion receptor: not what everyone expected it to be". Microbes Infect 14 (13): 1205–10. PMID 22884716. doi:10.1016/j.micinf.2012.07.015.
- Mastrangelo P, Hegele RG (March 19, 2013). "RSV fusion: time for a new model". Viruses 5 (3): 873–85. PMID 23518574. doi:10.3390/v5030873.
- Shakeri A, Mastrangelo P, Griffin JK, Moraes TJ, Hegele RG (November 6, 2014). "Respiratory syncytial virus receptor expression in the mouse and viral tropism". Histol Histopathol. Epub ahead of print. PMID 25374027.
- Tawar, RG; Duquerroy, S; Vonrhein, C; Varela, PF; Damier-Piolle, L; Castagné, N; MacLellan, K; Bedouelle, H; Bricogne, G; Bhella, D.; Eléouët, J.-F.; Rey, F. A. (2009). "Crystal structure of a nucleocapsid-like nucleoprotein-RNA complex of respiratory syncytial virus". Science 326 (5957): 1279–83. PMID 19965480. doi:10.1126/science.1177634.
- Money, VA; McPhee, HK; Mosely, JA; Sanderson, JM; Yeo, RP (2009). "Surface features of a Mononegavirales matrix protein indicate sites of membrane interaction". Proceedings of the National Academy of Sciences of the United States of America 106 (11): 4441–6. PMC 2657372. PMID 19251668. doi:10.1073/pnas.0805740106.
- Tan L, Lemey P, Houspie L et al. (2012). Leung, Frederick C. C, ed. "Genetic Variability among Complete Human Respiratory Syncytial Virus Subgroup A Genomes: Bridging Molecular Evolutionary Dynamics and Epidemiology". PLoS ONE 7 (12): e51439. PMC 3517519. PMID 23236501. doi:10.1371/journal.pone.0051439.
- "Respiratory syncytial virus (RSV)". A.D.A.M. Medical Encyclopedia, PubMed Health. National Center for Biotechnology Information, U.S. National Library of Medicine. January 2011.
- Chu, H. Y.; Kuypers, J.; Renaud, C.; Wald, A.; Martin, E.; Fairchok, M.; Magaret, A.; Sarancino, M.; Englund, J. A. (2013). "Molecular epidemiology of respiratory syncytial virus transmission in childcare". Journal of Clinical Virology 57 (4): 343–350. PMID 23684816. doi:10.1016/j.jcv.2013.04.011.
- Kim, HW; Canchola, JG; Brandt, CD; Pyles, G; Chanock, RM; Jensen, K; Parrott, RH (1969). "Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine". American Journal of Epidemiology 89 (4): 422–34. PMID 4305198.
- Ventre, Kathleen; Randolph, Adrienne (2007). "Ribavirin for respiratory syncytial virus infection of the lower respiratory tract in infants and young children". In Ventre, Kathleen. Cochrane Database of Systematic Reviews (1). pp. CD000181. PMID 17253446. doi:10.1002/14651858.CD000181.pub3.
- Kuzik, BA; Al Qadhi, SA; Kent, S; Flavin, MP; Hopman, W; Hotte, S; Gander, S (2007). "Nebulized hypertonic saline in the treatment of viral bronchiolitis in infants". The Journal of pediatrics 151 (3): 266–70, 270.e1. PMID 17719935. doi:10.1016/j.jpeds.2007.04.010.
- Mandelberg, A.; Tal, G; Witzling, M; Someck, E; Houri, S; Balin, A; Priel, IE (2003). "Nebulized 3% Hypertonic Saline Solution Treatment in Hospitalized Infants With Viral Bronchiolitis". Chest 123 (2): 481–7. PMID 12576370. doi:10.1378/chest.123.2.481.
- Bourke TW, Shields MD. Bronchiolitis. BMJ Clinical Evidence. 2011;04:308
- Handforth, J.; Sharland, M; Friedland, JS (2004). "Prevention of respiratory syncytial virus infection in infants". BMJ 328 (7447): 1026–7. PMC 403830. PMID 15117767. doi:10.1136/bmj.328.7447.1026.
- http://c.ymcdn.com/sites/www.aazv.org/resource/resmgr/IDM/IDM_Respiratory_Syncytial_Vi.pdf American Association of Zoo Veterinarians Infectious Disease Committee Manual 2013, CHIMPANZEE CORYZA/RESPIRATORY SYNCYTIAL VIRUS (RSV), Allison Wack, December 26, 2010, updated March 19, 2013.
- PreemieCare information and support on premature infants including in-depth resources on RSV and our comprehensive NICU Glossary.
- Synagis (registered to MedImmune, manufacturer of Synagis)
- Virazole (registered to Valeant Pharmaceuticals, manufacturer of Virazole)
- The Family Doctor
- RSV in Infants: Information includes symptoms, treatment, and prevention
- Biotrin providers of RSV kits
- Control of Communicable Diseases in Man. American Public Health Association.