Respiratory Syncytial Virus (RSV): Replication, Pathogenesis

Respiratory syncytial virus (RSV), is a member of the genus Pneumovirus within the family Paramyxoviridae.  RSV usually causes mild, cold-like symptoms. Most people recover in a week or two, but RSV can be serious, especially in infants and older adults.

RSV is a most common cause of pneumonia and bronchiolitis in infants and young children.

REPLICATION

Genome: single-stranded negative-sense RNA
Polymerase: viral encoded RNA-dependent RNA polymerase
Site of replication: cytoplasm of the host cell

  1. RSV attaches to host cells via the surface glycoprotein.
  2. Virion envelope fuses with the cell membrane by the action of fusion glycoprotein and enters the cell.
  3. Release the genome RNA and RNA-dependent RNA polymerase into the cytoplasm.
  4. The polymerase uses the genome as a template to produce capped and polyadenylated mRNAs
  5. mRNAs are translated into viral proteins
  6. Antigenome and genome RNAs are produced
  7. The resulting genomes are assembled with other viral proteins and buds from the plasma membrane to produce progeny virus particles.

Pathogenesis

  • RSV replication occurs initially in epithelial cells of the nasopharynx. Virus may spread into the lower respiratory tract and cause bronchiolitis and pneumonia.Bronchiolitis Image source: US National library of medicine
  • There is lymphocyte migration, resulting in peribronchiolar infiltration; submucosal tissues become edematous; and plugs consisting of mucus, cellular debris, and fibrin occlude the smaller bronchioles. Viral antigens can be detected in the upper respiratory tract and in shed epithelial cells in the plugs but are seldom detected in the small bronchioles.
  • Viremia occurs rarely if at all.
  • The incubation period of RSV infection is of 3-5 days.
  • Viral shedding may persist for 1-3 weeks in infants and young children, whereas adults shed for only 1-2 days.
  • High viral titers are present in respiratory tract secretions from young children.
  • Inoculum size is an important determinant of successful infection in adults (and possibly in children as well).
  • An intact immune system seems to be important in resolving an infection, as patients with impaired cell-mediated immunity may become persistently infected with a respiratory syncytial virus and shed the virus for months.

Signs and Symptoms 

  • The spectrum of respiratory illness caused by RSV ranges from inapparent infection or the common cold through pneumonia in infants to bronchiolitis in very young babies
  • About one-third of primary RSV infections involve the lower respiratory tract severely enough to require medical attention. The child may wheeze.
  • Almost 2% of infected babies require hospitalization with peak occurrences at 2 months of age.
    • Progression of symptoms may be very rapid, culminating in death (with the availability of modern pediatric intensive care, the mortality rate in normal infants is low.)
    • But if  RSV infection is superimposed on pre-existing diseases, such as congenital heart disease, the mortality rate may be high.
  • Infections in the elderly may cause symptoms similar to the influenza virus infection. Pneumonia may develop.
  • Children who suffered from RSV bronchiolitis and pneumonia as infants often exhibit recurrent episodes of wheezing illness for many years.
  • RSV is an important cause of otitis media (It is estimated that 30-50% of wintertime episodes in infants may be due to respiratory syncytial virus infection).

Laboratory Diagnosis

Specimens should be collected using flocked nylon swabs (cotton-tipped or calcium alginate swabs are not suitable) and placed immediately in the viral transport medium (VTM). Preferred samples are:

Isolation of the virus and detection of viral antigens in respiratory secretions is the procedure of choice to diagnose respiratory syncytial virus infection.

Respiratory syncytial virus differs from other paramyxoviruses in that it does not have a hemagglutinin; therefore, diagnostic methods can not use hemagglutination or hemadsorption assays.

Antigen (Ag) detection 

  • Direct identification of viral antigens in clinical samples is rapid and sensitive.
  • Immunofluorescence on exfoliated cells or ELISA on nasopharyngeal secretions is commonly used.
  • Large amounts of virus are present in nasal washes from young children but much less is present in specimens from adults.
  • ELISA kits are useful for rapid diagnosis, which is desirable because antiviral therapy is available.

Isolation and identification of the virus

  • Inoculate the sample into cell cultures immediately; freezing of clinical specimens may result in complete loss of infectivity (labile virus). Commonly used cell lines are; human heteroploid cell lines; HeLa and Hep-2.
  • The presence of RSV can usually be recognized by the development of giant cells and syncytia in inoculated cultures. It may take as long as 10 days for cytopathic effects to appear.
  • Definitive diagnosis can be established by detecting viral antigens in infected cells using a defined antiserum and the immunofluorescence test.
  • Rapid isolation of RSV can be achieved by spin-amplified inoculation of vials containing tissue cultures growing on coverslips. Cells can be tested 24-48 hours later by immunofluorescence.
  • Detection of RSV is strong evidence that the virus is involved in a current illness because it is almost never found in healthy people.

Serology

Nucleic Acid Detection 

Detection of the genome of RSV in respiratory secretions using PCR.

  • Subtyping of respiratory syncytial virus
  • Analysis of genetic variation in outbreaks.

Prevention and Control

Protect your child from RSV (Source: CDC)

Protect your child from RSV

  1. Avoid close contact with sick people.
  2. Wash your hands often.
  3. Cover your coughs & sneezes.
  4. Avoid touching your face with unwashed hands.
  5. Stay home when you’re sick.

References and further reading

Acharya Tankeshwar

Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. As an asst. professor, I am teaching microbiology and immunology to medical and nursing students at PAHS, Nepal. I have been working as a microbiologist at Patan hospital for more than 10 years.

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