Human respiratory syncytial virus

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A Microbial Biorealm page on the genus Human respiratory syncytial virus


Higher order taxa

Viruses; ssRNA viruses; ssRNA negative-strand viruses; Mononegavirales; Paramyxoviridae; Pneumovirinae; Pneumovirus


NCBI: Taxonomy

Human respiratory syncytial virus

Description and significance

Human Respiratory Syncytial Virus was first isolated in 1956 from a laboratory chimpanzee with a respiratory illness and was later discovered to be of human origin (1). RSV consists of two antigenic subtypes, A and B. Subtype B is characterized as the asymptomatic strains that of which the majority of individuals experiences. The more severe illnesses and which usually predominate during outbreaks are associated with subtype A strains(8). RSV was determined to be the leading cause of lower respiratory tract infections particularly in young infants. The severity of the disease is very diverse ranging from mild cold symptoms to severe and life-threatening. It's the leading cause of pneumonia and bronchiolitis in infants. It may cause mortality or morbidity in the elderly as well as immunodeficient individuals. It is the most common pathogen leading to hospitalization in young children up to the age of 5. Approximately two thirds of infants are infected with RSV within their first year and 90% have been infected by the age of 2(1).

Genome Structure and Virion Structure

The genome of RSV was completely sequenced in 1997. It is a linear single stranded negative-sense RNA consisting of 15,191 base pairs. The genome is found in the helical nucleocapsid. The genome encodes for 11 proteins including structural and non-structural(2).

The virion of the RSV is enveloped with a lipid bilayer, which is obtained from the host’s plasma membrane. It contains three surface glycoproteins, the attachment protein G, fusion protein F, and the small hydrophobic SH protein, which are separated from each other and can be seen as “spikes” that project out of the virion. The glycoproteins can be measured to be about 11-20nm in size, while the virion appears to be about 150-300nm in diameter(2).

The major function of the F protein is to direct viral penetration by the fusion between the virion and the host plasma membrane. The F protein is also able to mediate fusion with other neighboring cells forming syncytia, when it is expressed on the cell surface. The glycoprotein, G, is a type II transmembrane glycoprotein and is the major RSV attachment protein(5). It contains a single hydrophobic region which serves as a signal peptide and also as a membrane anchor. The small hydrophobic SH protein is a short integral membrane protein whose function is unknown. However, it is suggested that the SH protein enhances the function of the attachment protein and or fusion protein. Another RSV protein is the matrix protein M, located in the inner layer of the lipid bilayer, and is found to play a role in the formation of virus-like particles. These four proteins are used to form the viral envelop. The non-structural proteins are NS1 and NS2, these proteins enhance viral growth but are not essential(2).

The virion consists of a nucleocapsid which is contained in the lipid bilayer. The nucleocapsid has a symmetrical helix shape and is measured to be about 12-15nm in diameter. There are four nucleocapsid proteins inside the virion which carry out the replication and transcription of the RSV genome, the nucleocapsid protein N, the phosphoprotein P, the antitermination factor M2-1, and the large polymerase subunit L(1).

The RSV nucleocapsid N protein binds to genomic and antigenomic RNA and forms an RNAse-resistant nucleocapsid. This provides protection of the viral RNA from the toll-like receptors and RNA recognition helicases that initiate immune responses. In order for the N protein to encapsidate minigenome RNAs the help of the P protein is required. The P protein acts as a chaperonin for the N protein, without it the N protein would be incapable to binding to minigenome RNA. The L protein is responsible for all enzymatic activity and the M2-1 protein is a transcription antitermination factor which is crucial for viral viability. Proteins M2-1 and M2-1 are both play important roles in balancing transcription and RNA replication(2).

Virus Life Cycle and metabolism

Respiratory Syncytial Virus enters the cell through fusion at the plasma membrane. The initiation step occurs when the G protein of the RSV binds to a certain long unbranched polysaccharide of the extracellular matrix consisting of disaccharide subunits called GAGs. GAGs are often involved in the interaction between cells and various viruses(3). The F protein then interacts with the protein RhoA and mediates the attachment of the virus. RhoA may act as a receptor for the fusion protein or may play a role in viral infection; the actual role of RhoA is unknown(2). Viral gene expression and replication occurs in the cytoplasm. Once the virus is in the cytoplasm the nucleocapsid and the genome is released. The M2-2 gene governs the transition from transcription to production of genomic RNA. The polymerase then enters the genome at its 3’ end and the genes are transcribed into mRNAs by the start-stop-restart synthesis. This creates a polar transcription gradient in which the promoter starting genes are transcribed more frequently than the genes which are downstream. Replication generates a complete positive-sense RNA complement of the genome called the antigenome, which acts as a template for genome synthesis(3). The genome and the antigenome are both coated with the N protein at all time which serves as the template for RNA synthesis. The M protein regulates the assembly of the RSV by interacting with the envelope proteins F and G and with the nucleocapsid proteins N, P, and M2-1. The new synthesized proteins then self-assembly and budding occurs, acquiring an envelop from the membrane.


Respiratory Syncytial Virus is spread through person to person contact by infected respiratory secretions. It requires the close contact of infected individuals, contact with infected nasal secretions, or contamination of hands or objects which have been introduced to such secretions. Outbreaks of the disease occur yearly at particular seasons, which usually last up to 5 months. Epidemics usually occur in the late fall, winter or spring seasons, with most outbreaks in February or March(1). RSV is commonly acquired by patients who are hospitalized and the likelihood of RSV infection increases with the duration of the stay. The hospital staff plays a major role in the spread of RSV infection. To reduce the risk of infection precautions must be in effect such as hand washing(2).


Respiratory Syncytial Virus infection pathology is similar to that of pneumonia and bronchiolitis. RSV causes severe damage to the epithelium and to the bronchiolar ciliary apparatus. This results in the collection of fluid in the bronchioles and alveoli. This in turn causes obstruction of the bronchioles and alveoli, causing collapse or emphysema of the airway(2).

RSV replication initiates in the nasopharynx and replicates primarily in the superficial layer of the respiratory epithelium. The time of infection to the onset of the illness is about 4 to 5 days. The virus spreads from the upper respiratory tract to the lower through the inhalation of secretions or spread by the respiratory epithelium. There have been cases which RSV has been found to spread to other organs such as the liver(1).

An infant who is introduced to RSV for the first time might only encounter mild symptoms which include coughing, rhinorrhea, and decreased appetite. Wheezing, sneezing, and a low-grade fever are also common symptoms at this stage. In this case the symptoms should not progress any further. In more severe cases the coughing and wheezing will worsen and the child might experience difficulty breathing. The child may refuse to eat, severe rapid breathing is usually evident and in extreme cases respiratory failure may occur(2).

Current Research

Human respiratory Syncytial Virus lacks an approved vaccine or an antiviral therapy. Studies with RSV are limited due to the poor growth of RSV in vitro, its instability, and lack of animal models.

A nucleoside analog was approved in 1986 for treatment of RSV called ribavirin. The treatment was clinically administered through an aerosol and was not associated with any long term effects. However there was little evidence that ribavirin improved long-term pulmonary function, lowered mortality rates, or decreased the duration of hospitalization. The use of ribavirin is now only under consideration for severe RVS infected patients. Studies still in progress for patients of high-risk(2).

The administration of RSV neutralizing antibodies are also being further studied. An intravenous infusion of RSV neutralizing antibodies into a healthy or high-risk infant infected with RSV was tested. The results of this showed a decrease in the level of virus shedding but there was little to no improvement clinically. A combination therapy with antibodies and ribavirin are being studied for further evaluation(2).

A study presented to use therapy with rhDNase, a mucolytic agent, was proved to be an effective therapy for treating RSV infection on the basis of improvements in the chest x-rays. The duration of hospitalization was not shown to have improved. Studies are required to further evaluate the use of rhDNase in the treatment of RSV(7).


1. Collins L., Peter, and Barney S. Graham. 2008. Viral and Host Factors in Human Respiratory Syncytial Virus Pathogenesis. Journal of Virology. 82: 2040–2055.

2. Collins L., Peter, Robert M. Chanock, and Brian R. Murphy. 2001. Respiratory Syncytial Virus. pg.1443-1475. Fields Virology. ed. David M. Knipe and Peter M. Howley. Philadelphia: Lippincott Williams and Wilkins pg. xi-3063

3. Cowton, M. Vanessa, David R. McGivern, and Rachel Fearns. 2006. Unravelling the complexities of respiratory Syncytial virus RNA synthesis. Journal of General Virology. 87: 1805-1821.

4. Enders, Gisela. 1996. Respiratory Syncytial Virus. Medical Microbiology edition 4. ed. Samuel Baron. The University of Texas Medical Branch, Galveston

5. Hacking, Doug and J. Hull. 2002. Respiratory Syncytial Virus-Viral biology and the host response. Journal of Infection. 45: 18-24.

6. Lazer, Issac, Carla Weibel, James Dziua, David Ferguson, Marie L. Landry, and Jeffery S. Kahn. 2004. Human Metapneumovirus and severity of respiratory Syncytial virus disease. Emerging Infectious Diseases. 10: 1318-1320.

7. Nasr, Samya Z., Peter J. Strouse, Errol Soskolne, Norma J. Maxvold, Kimberly A. Garver, Bruce K. Rubin, and Frank W. 2001. Efficacy of Recombinant Human Deoxyribonuclease I in the Hospital Management of Respiratory Syncytial Virus Bronchiolitis. Chest 120.1: 203. 

8. Oliveira TFM, Freitas GRO, Ribeiro LZG, Yokosawa J, Siqueira MM, Portes SAR. 2008. Prevalence and clinical aspects of respiratory syncytial virus A and B groups in children seen at Hospital de Clínicas of Uberlândia, MG, Brazil. Mem. Inst. Oswaldo Cruz 103: 417-422.

Edited by Meaghan Andre student of Emily Lilly at University of Massachusetts Dartmouth.