62325 Virology Lecture 8 Respiratory Syncytial Virus

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62325 Virology Lecture 8Respiratory Syncytial
Virus

• Dr Mike Kotiw

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http//www.rsvinfo.com/
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RSV Lecture aims

• To understand the structure of RSV
• To understand the significance of and disease
  caused by RSV
• To understand how the RSV infection may be
  diagnosed
• To understand the therapeutic options available
  in the treatment of RSV infection

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RSV overview

• In Australia, 50 of infants contract RSV
  infection within the first year of life
• In the US, effect of annual outbreaks of RSV
  infections
• 90,000 infants being hospitalised
• 4500 deaths
• Cost to the US economy from RSV infections 300
  billion pa.

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RSV overview

• Infected infants lt2 months of age
• about 50 develop bronchiolitis
• of which some 25 require hospitalisation
• mortality in this sub-group about 1
• Recovery from natural exposure does not always
  confer protective immunity
• But subsequent infections may be less severe.

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RSV overview

• RSV in otherwise healthy adults associated with
  common cold like symptoms
• Major issue is LRTI and bronchiolitis pneumonitis
  in children lt1 year old
• Outbreaks tend to be annual and usually in the
  later winter months

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RSV clinical features

• Colds
• the most common manifestation, usually in lt5 year
  olds
• can affect elderly or immunocompromised

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RSV clinical features

• Bronchiolitis
• seen in infants, generally lt6 months of age
• starts with nasal obstruction with mucus and
  discharge -gt develops into LRTI
• followed by fever, respiratory distress and
  expiratory wheezing

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RSV clinical features

• Pneumonia
• Mainly small infants
• Much like bronchiolitis but without expiratory
  wheezing

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RSV virology

• Pneumovirus of the paramyxoviruses
• There is 1 serological type
• Little genomic homology between RSV
  (pneumoviruses) and other paramyxoviruses
• although replicative pathways appear the same

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RSV virology

• ssRNA virus (negative sense RNA)
• Pleomorphic enveloped particle of 90-130 nm with
  helical symmetry
• ssRNA genome of about 15kb which codes for 10
  proteins (compared with the more common 6-7 of
  other paramyxoviruses)

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RSV virology

• Major features include
• a nucleoprotein (N) associated nucleoproteins
• a phosphoprotein (P)
• a polymerase (L)
• a fusion glycoprotein (F)
• an attachment glycoprotein (G)

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RSV virology

• Maturation dependent on interactions between two
  matrix proteins (M and M2) and a hydrophobic
  protein (SH)
• Two other proteins (NS1 and NS2) have been
  isolated but functions are yet to be determined
• Grows in cells (HeLa and Hep2also a HeLa like
  cell line) with syncytial CPE
• Is HA negative

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http//www.tulane.edu/dmsander/WWW/335/Paramyxovi
ruses.html
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http//www.tulane.edu/dmsander/WWW/335/Paramyxovi
ruses.html
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RSV diagnosis

• Diagnostic procedures include
• fluorescent antibody tests
• reverse transcriptase polymerase chain reaction
  (RT-PCR)
• ELISA,
• rapid chromogenic immuno-tests for antigen
• virus islolation.

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RSV diagnosis

• Can be demonstrated directly using IFT on NPAs
• RSV can be isolated from
• mouth washings
• nasal secretions (need to avoid freezing
  specimens as virus is inactivated)

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RSV diagnosis

• NPA inoculated onto HeLa or HEP2 cells and
  examined for CPE
• Virus isolation in cell culture is the gold
  standard (Hep2, Hela and embryonic respiratory
  cells)
• virus is heat labile with assays relying less on
  viral viability often more effective

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RSV therapy

• Supportive treatment mainstay for patients with
  mild infections
• Ribovarin has been used successfully in acute
  cases efficacy???
• Potential therapies include
• anti RSV IgG (IV nasal instillation)
• antisense RNA chimeras
• ribozymes directed at cleaving viral mRNA.

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RSV therapy

• Vaccines have been problematical
• Original use of inactivated virus led to immune
  complex formation on wild type challenge
• Current efforts sub unit vaccines include
  purified fusion proteins using the F glycoprotein
  as the antigen.
• These vaccines have been trialed in children but
  with mixed outcomes.