Reference Work Entry

Encyclopedia of Molecular Mechanisms of Disease

pp 1835-1836

Respiratory Syncytial Virus

  • Richard J. SugrueAffiliated withDivision of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University

Synonyms

RSV; Human RSV; HRSV

Definition and Characteristics

Although human respiratory syncytial virus (HRSV) was first reported in infants exhibiting respiratory distress in 1957 [1], it is now recognised as one of the most important causes of lower respiratory tract infection in young children. The virus is spread in respiratory droplets, and transmission can occur either directly during close contact between individuals, or by contact with contaminated surfaces. In temperate climates HRSV epidemics are seasonal, usually occurring from late autumn until early spring. In tropical climates HRSV infections occur through-out the year, but an increase in the HRSV infection rate is observed during the rainy seasons. Although the disease symptoms are usually relatively mild in healthy adults, severe complications, including bronchial pneumonia and respiratory failure, can occur in certain high-risk groups. These include neonates and premature babies, the elderly, and individuals with impaired immune and cardiac systems [2].

Prevalence

Evidence suggests that by the age of 4, virtually all children have developed antibodies against HRSV, and that re-infection with HRSV occurs throughout adolescence and in later life.

Genes

HRSV is grouped within the family paramyxoviridae, subfamily pneumovirinae, genus pneumovirus. The virus genome (vRNA) is a single-stranded non-segmented RNA molecule of negative polarity, which encodes for eleven virus proteins [3]. A leader (Le) region and trailer (Tr) region flank the vRNA at the 3′- and 5′ ends respectively, and transcription of the vRNA is initiated at the 3′ end. The vRNA contains ten individual genes (Fig. 1a), and each gene contains an open reading frame (ORF) that is flanked by a gene start (GS) and gene end (GE) sequence. With the exception of the M2 gene, which encodes the M2–1 and M2–2 proteins, each gene is transcribed and translated to give a single virus protein (Fig. 1b, c).
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Respiratory Syncytial Virus. Figure 1

HRSV genome structure and molecular architecture. (a) A schematic diagram showing the organisation of the virus genome. The gene order and location of the leader (Le) and trailer (Tr) sequences are indicated. (b) The virus genome gives rise to eleven virus proteins whose function and location are indicated. (c) A schematic diagram showing the molecular organisation of a mature HRSV particle.

Most of the virus genes are arranged contiguously within the vRNA, and adjacent genes are separated by intergenic sequences. In the case of the M2 and L genes, the GE sequence for the M2 ORF is located after the GS of the L gene, thus creating an overlap between these genes. Transcription of an ORF is started at the GS sequence, and once the GE sequence is reached, the polyadenylated virus mRNA is released from the vRNA. The virus polymerase scans through the intergenic region until the GS sequence of the adjacent gene is reached and transcription of the ORF is reinitiated. The genes encoding the nonstructural proteins NS1 and NS2 are unique to members of the genus pneumovirus, while the M2 gene is found in other members of the subfamily pneumovirinae, which includes the genus metapneumovirus.

Molecular and Systemic Pathophysiology

Several studies have shown that the expression of a number of specific proinflamatory cytokines, including interleukin 8 (IL8), MIP-1 and RANTES, are increased in humans infected with HRSV. Animal studies have demonstrated that HRSV infection leads to an enhanced chemokine expression in the lung, leading to lung eosinophilia. This has suggested that the induction of proinflamotory cytokines in the lower respiratory tract is a major factor in the appearance of severe manifestations of the disease in infected patients [4]. Data from several groups have suggested that the severity of HRSV infection may also be linked to co-infection with human metapneumovirus (HMPV). Although HMPV has been detected in patients with severe respiratory distress caused by HRSV, its role in HRSV pathogenesis has yet to be confirmed. There has been an increasing body of information that HRSV is able to counter the host’s innate anti-virus immune response during infection by inhibiting interferon type 1 signaling, a process that involves the NS1 and NS2 proteins.

Diagnostic Principles

The traditional and routine procedure for diagnosing potential HRSV infection involves virus antigen detection in nasopharyngeal aspirates using an immunofluorescence based assay. Alterative procedures include the detection of viral RNA in patients samples using the real time reverse transcriptase-polymerase chain reaction (RT PCR), and monitoring the appearance of HRSV antibodies in patients serum.

Therapeutic Principles

There is currently no licensed vaccine to protect individuals from HRSV infection, although several vaccines generated by recombinant DNA technology are under development. The current preventative measures include good personal hygiene and passive immunization. Although the intravenous injection of human immune globulin with high titers of neutralizing HRSV antibody is an option (e.g. RespiGam®), the use of humanized neutralising HRSV monoclonal antibodies (e.g. Synagis®) remains the most effective method of protecting high-risk patients. However, the high cost of using Synagis has restricted its widespread use. Although ribavirin is licensed to treat infected individuals, results obtained during carefully controlled clinical studies have questioned its usefulness. In some cases a combination of ribavirin and immune globulin with high titers of neutralizing HRSV antibody has been effective in treating patients. It is worth noting that alternative antivirus strategies are currently in development, which includes the use of peptides and small molecules that inhibit virus entry, and the use of specific siRNA molecules that can prevent the expression of vital virus gene products.

Copyright information

© Springer-Verlag GmbH Berlin Heidelberg 2009
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