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Common colds virii
- 30-50% - Rhinoviruses (Picorna-)
- 10-30% - Coronaviruses
- 10-15% - Adenoviruses
- Caused by 200+ types of viruses
- No vaccines
- No anti-viral drug
- continuous 3+ billion cost per year
- annual frequencty decreases with age
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Picornaviruses
- - non-enveloped
- - ss (+)RNA genome, IRES
- Both Rhino- and Entero- can be causes for common colds but Rhino is much more common.
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Enterovirus
- picornavirus
- Acid resistant
- 37C optimum growth temp
- oral-fecal transmission
- gut primary infection site
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Rhinovirus
- Picornavirus
- Labile Acid sensitivity
- 33C optimum temp
- aerosol and fomites(contaminated objects) transmission
- wash hands
- respiratory tract primary
- antibody only good for 1 type (of >100)
- no anti ddrug
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Coronaviruses
- (+) RNA genome
- Enveloped
- Human coronaviruses
- - 1/3 of common cold
- SARS
- no vaccine or anti-corona
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SARS
- 2002 South China
- A new syndrome observed in late 2002 in southern China
- June, 2003 - 8,000 cases worldwide and 775 deaths
- Last outbreak was in 2004 from laboratory
- quarantine travelers w fever
- 1/3 of original cases came from food handlers
- A closely related coronavirus was found in bats
- Directly transmit to humans, evolve in humans to
- facilitate human-to-human transmission
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Adenoviruses
- dsDNA genome
- non-enveloped
- first recognized among military recruits during 1950-60 (World War II)
- Since 1999, 10-12% of recruits became infected.
- Transmission through via respiratory droplets and fecal matter
- Most immunocompetent patients have a full recovery
- Most are asymptomatic.
- Most people have been infected with at least 1 type by age 15
- Oral vaccine of live attenuated adenoviruses was used since 1971, but discontinued in late 1990
- Oral vaccine of type 4 and 7 in FDA approval review
- No anti-adeno drugs
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Paramyxoviruses
- (-) RNA genome
- Enveloped
- Fusion protein (syncytia)
- Attachment protein
- Parainfluenza viruses (type 1-4)
- Respiratory syncytial virus (RSV)
- Major cause of severe respiratory infection in infants and young children (<3 year-old="" br="">Asymptomatic in most cases
- mild-cold like symptoms (upper respiratory tract)
- - older children and adults
- Complications
- bronchitis/bronchiolitis in young children
- 1st cause for Croup (laryngotracheobronchitis)
- - swelling at the voice box, “barking” cough
- No antiviral drug/No vaccine
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Croup
- laryngotracheobronchitis
- Paramyxovirus 1st cause
- swelling at the voice box, “barking” cough
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RSV
- Respiratory Syncytial virus
- Milder symptoms in older children and adults
- Complications
- Bronchiolitis/bronchitis in young children
- 1st cause for Infantile bronchiolitis/pneumonia
- 100,000 hospitalizations, 4,500 deaths/year in US
- 1st cause for fatal respiratory tract infection in infants
- Diagnosis-Rapid detection of RSV antigen from nasopharyngeal aspirates.
- Antiviral drugs
- Ribavirin – anti-viral RNA polymerase, used only in persons at high risk for severe disease (premature and immunocompromised infants)
- Passive immunization (high risk groups)
- RespiGam – pooled human serum containing anti-RSV antibody
- Synagis – antibody against F protein of RSV
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RSV Therapies
- Antiviral drugs
- Ribavirin – anti-viral RNA polymerase, used only in persons at high risk for severe disease (premature and immunocompromised infants)
- Passive immunization (high risk groups)
- RespiGam – pooled human serum containing anti-RSV antibody
- Synagis – antibody against F protein of RSV
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Flu Pandemics
- 1918-19 Spanish Flu (H1N1)
- 20-50 million deaths worldwide
- >500,000 U.S. deaths
- Less deadly as time goes on
- 2009 (H1N1)
- < 20,000 deaths
- pandemic resulting from subtypes of hemagglutinin neuraminidase
- come from birds(natural resevoir) many more strains that may become human
- pigs/human infection both ways and can recombine(genetic reassortment)
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Influenza virus
- (-)RNA, 8 segments
- enveloped
- HA – attachment
- NA – virion release
- M2 – uncoating
- Three types
- A (mammals and birds)
- B (mammals)
- C (mammals)
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Life cycle of influenza viruses
- RNA replication in the nucleus
- The HA has several functions:
- viral attachment protein, binding to sialic acid on epithelial cell surface receptors
- promotes fusion of the envelope to the cell membrane;
- hemagglutinates red blood cells
- The proton channel formed by the M2 protein promotes acidification of the envelope contents to break the protein-protein interactions to allow uncoating and delivery of the nucleocapsid into the cytoplasm.
- -other RNA viruses replicate in the cytoplasm;
- in contrast, influenza goes into the nucleus
- -virus attaches to cell surface via hemagglutinin, then uses endosomal pathway;
- it exits endosome using the M2 protein > genetic material is released, which enters nucleus
- -for this particle to be released, you need neuraminade at surface- so virus can be released to infect other cells
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Pathogenesis of influenza viruses
- virus first targets and kills mucus-secreting, ciliated, and other epithelial cells, causing the loss of this primary defense system.
- NA facilitates the development of the infection by cleaving sialic acid residues of the mucus, thereby providing access to tissue.
- If the virus spreads to the lower respiratory tract, the infection can cause severe desquamation (shedding) of bronchial or alveolar epithelium down to a single-cell basal layer or to the basement membrane.
- In addition to compromising the natural defenses of the respiratory tract, influenza infection promotes bacterial adhesion to the epithelial cells.
- Pneumonia may result from a viral pathogenesis or from a secondary bacterial infection.
- Influenza may also cause a transient or low-level viremia but rarely involves tissues other than the lung.
- -how does virus cause disease? It comes in through aerosol inoculation, entering & replicating in respiratory tract; in respiratory tract, it kills cells, so that there is temporary dysfunction; the immune response is stimulated to fight against viral infection- depending on how fast viral replication & immune response is, there may or may not be symptoms at this point; sometimes, the virus travels into the lower respiratory tract to cause pneumonia; when the virus is replicating and killing cells in the respiratory tract, you also make it more vulnerable to bacterial infection- dysfunction due to infection causes loss of ability to fight bacterial infection; in rare cases, viruses spread to blood, which spreads the virus to other organs (causing complications, ex. in brain)
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Complications of Flu
- 36,000 deaths/year US high risk elderly (>65 years)
- Pneumonia (elderly, young, immunocomp)
- 1. viral
- 2. bacterial
- Non-pulmonary
- -CNS(young)
- -cardiac (myocarditis/pericarditis) (old)
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anti-flu immunity
- anti-HA antibody -but flu evolves (antigen drift)
- flu-specific cytotoxic lymphocytes(T-cells)
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antigen drift
- errors during RNA replication
- Minor changes in HA/NA
- the pre-existing antibody does not work
- outbreak occurs
- continuous process
- vaccine strains must be updated
- Direct transmission of
- animal influenza A to
- humans
- Genetic reassortment
- (gene swapping)
- Major changes in HA/NA
- pandemics occurs
- (new, spreading globally, but not necessarily deadly)
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Flu Nomenclature
- virus type,
- geographic origin
- strain number- sometimes not present
- year of isolation
- virus subtype
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Influenza vaccine
- Killed virus (grown in eggs)-> Ab only
- - short-lived protective effects
- - need to decide which strain to use by February
- A/Brisbane/10/2007 (H3N2)
- A/Brisbane/59/2007 (H1N1)
- B/Florida/4/2006
- Live attenuated (cold-adapted, grown in eggs)-> Ab and CTL(cytotoxic lymphocytes)
- - limited in upper tract
- - FluMist (nasal spray)
- - mucosal immunity
- - only to healthy individuals
- -could provide spectrum (blanket) protection
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Human H5N1 cases
- example of different pathologies- different rate of killing, different timelines
- rare, contact with sick/dead poultry
- deadly
- rare man-to-man transmission
- little immunity for humans
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