Respiratory Syncytial virus (RSV) - MegaMicro

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Respiratory Syncytial virus (RSV)

Microbiology > Virology > RNA viruses > Single Stranded RNA viruses > Paramyxovirus
 
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1. Structure
a. Paramyxoviridae (Pneumovirus) family
b. Negative-sense ssRNA surrounded by helical nucleocapsid
c. Enveloped:
i. Lipid bilayer from host’s plasma membrane
ii. Glycoprotein projections: the attachment protein G, fusion protein F, and the small hydrophobic SH protein
d. 150-300nm in diameter

2. Pathobiology
a. Physiology
i. Transmitted via aerosol or contact via nasal secretions
ii. RSV replication initiates in the nasopharynx and replicates primarily in the superficial layer of the respiratory epithelium
iii. Virus spreads from the upper respiratory tract to the lower through the inhalation of secretions or spread by the respiratory epithelium
1. Enters bronchiolar and alveolar epithelium
2. Damages epithelium and to the bronchiolar ciliary apparatus
3. Syncytia are formed when the membranes of the infected cells fuse with adjacent cells to form a large, multinucleated mass of cells
4. In the bronchioles, mucosal edema, mucin secretion and bronchiolar lumina with dead epithelial debris causes obstruction
5. Leads to obstruction of airways and causes collapse or emphysema
iv. 4-5 day incubation period
b. Virulence factors
i. Enveloped virus
ii. Glycoproteins assist in cell entry
iii. Encoded viral proteins prevent T cell activation by secreting cytokines and chemokines that inhibit synapse assembly with dendritic cells
iv. Viral protein G induces large amounts of cytokines from CD4 T cells, mast cells, basophils and monocytes – increased inflammation may cause asthma attacks
v. Virus can survive on hard environmental surfaces for several hours
c. Tropism: bronchiolar and alveolar epithelium
d. Hosts: humans only
e. Lifecycle
i. Initial entry into respiratory epithelium
1. G protein of the RSV binds to a certain long unbranched polysaccharide of the ECM consisting of GAGs.
2. F protein then interacts with the protein RhoA and mediates the attachment of the virus
ii. Viral gene expression and replication occurs in the cytoplasm.
1. M2-2 gene governs the transition from transcription to production of genomic RNA
2. Replication generates a complete positive-sense RNA complement of the genome called the antigenome to act as a template for genome synthesis
3. The genome and the antigenome are both coated with the N protein
4. M protein regulates the assembly of the RSV by interacting with the envelope proteins F and G and with the nucleocapsid proteins
iii. New synthesized proteins self-assemble and budding occurs, acquiring viral envelope from the host membrane

3. Epidemiology
a. Reservoir: Human (90% of infants infected by age 2)
b. Classically a disease of the very young, however older adults may devlope acute illness as well.

4. Disease manifestations
a. 20-40% may involve lower respiratory tract
i. pneumonia
ii. bronchiolitis
b. common cold

5. Diagnosis
a. Suspected based on the time of year of the infection – prevalence usually coincides with the winter flu season
b. Symptoms consistent with upper respiratory tract infection – can include rhinorrhea, pharyngitis, cough, headache, fatigue, and fever
c. Infants and high-risk adults with certain chronic illnesses or immunosuppression may have more severe complications such as pneumonia
d. Physical exam findings: wheezing, hypoxemia
e. Chest X-rays: typical bilateral perihilar fullness of bronchiolitis
f. Laboratory
i. Rapid antigen detection assays from respiratory secretions
ii. ELISA for viral antigens (nasal washing)
iii. RT-PCR assay (especially for older children and for adults) to detect viral RNA


6. Differential diagnosis
  • Human metapneumovirus
  • Influenza virus
  • Parainfluenza virus
  • Bacterial pneumonia
  • Neonatal sepsis
  • Enterovirus-D68

7. Therapy
a. Generally Supportive therapy for otherwise healthy infants: ensure adequate oxygenation, ventilation, nutrition, and hydration
b. High-risk infants and adults require closer observation
d. Severe cases may benefit from albuterol and aerosolized ribavirin

8. Prevention and control
a. Contact precautions, hygiene, clean environmental surfaces
b. Isolation in hosptial environment
c. Immunoprophylaxis with anti-RSV immunoglobulin or monoclonal antibody [palivizumab] is available for infants at high risk (very expensive)
d. Vaccine is not available



Related concepts
common cold
Palivizumab
bronchiolitis

Web links:  http://www.cdc.gov/rsv/clinical/index.html  - CDC info on RSV
 
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