Influenza Viruses Flashcards
What is the history of Influena?
- Influenza has been described as early as 400 bc.
- Major epidemics and pandemics of influenza have occurred throughout history.
- Many virologists think another influenza pandemic that could kill millions of humans is inevitable.
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What is the epidemiology of influenza?
Epidemics become unmanageable at alarming speeds because:
- Short incubation period (1-4 days)
- One droplet can contain 100,000 to 1,000,000 virus particles
- Symptomatic people do not stay home =spread
- Lack of herd immunity
Absenteeism from schools is the best indicator of the scale of an epidemic.
What are the statistics of Influenza?
- 1957–1987: 20 influenza epidemics were recorded in the United States
- > 200,000 people in the US are hospitalized each year for respiratory and heart conditions illnesses associated with seasonal influenza virus infections
- 36,000–50,000 people have died as a direct or indirect consequence of an influenza infection annually
What is involved in the 1918 Influenza Pandemic?
- Also called the Spanish flu
- Killed 675,000 Americans; 50-100million people worldwide
- National average death rate was 4.39 out of every 1000 people
- Unique epidemic: healthy adults ages 20-40 died of the flu, in addition to children and elderly ( who are usually high-risk)
- It decreased the life expectancy in the US by 11 years
- Close troop quarters and massive troop movements hastened the pandemic
- John Barry’s “The Great Influenza”
What are the clinical features of Influenza?
Uncomplicated Infection
Onset of symptoms:
- Heachache
- Aching in the limbs and back
- Fever (100-103)
- Malaise
- Dry cough
- Tickling throat
- Sore throat
- Myalgia
- Chest x-ray is normal
Usually resolves itself after 7 days.
What are the clinical features involved in complicated infection?
- Age-dependent
- Young children: croup, secondary bacterial pneumonia, middle ear infections
- Elderly: life-threatening secondary bacterial pneumonia, pre-existing conditions like congestive heart disease exacerbated
- Immune compromised individuals at risk of death during an influenza epidemic
What is Reye’s Syndrome?
- Rare condition
- Risk of developing Reys’s syndrome increases with aspirin use
- R.S. affects all organs of the body
Most harmful to the brain and liver
Casues pressure in the brain and massive accumulation of fat in the liver and other organs
What is the classification of Influenxa viruses?
- Orthomyxoviridae family
- 3 types of influenza: A, B and C
- All 3 can infect and cause similar symptoms in humans.
- Infection with one type does not confer immunity to another type of influenza.
What is the laboratory Diagnosis of Influenza?
Office-based rapid tests: ELISA assays
- Some can distinguish between influenza A and B
- Fast results: 1 to 20 minutes
- Some false-positive or negative results
Other tests
- Cell culture: inoculate MDCK cells, most accurate test
Serology
- Analyze convalescent serum and analyze for an increase in antibody titer
“Flu chips” or microarrays
- Microarray detection panel used during 2009 H1N1 pandemic
- Glycan microarray analysis
What is the cellular pathogenesis of the virus?
- Droplet transmission
- Virus enters repiratory tract
- Attaches to ciliated columnar epithelial cells lining the sinuses and airways
What is the Influenza Pathogensis?
- Primary site of infection: tracheobronchial tree, involving nasopharynx
- As virus replicates, cilia are destroyed.
Cleaning system in the lungs does not work as well.
More mucus stays in the airway, clogging them and causing coughing.
- Destruction of cilia contribute to secondary bacterial pneumonia infections, sinusitis, otitis
What is the Humoral Immunity?
What are Mucosal Antibodies?
- Secretory antibodies are the first line of defense
- IgA in the upper respirator tract
- Accumulates in mucosal secretions
- Stimulated by nasal vaccine
- IgG involved in systemic protection
What is Cellular Immunity against influenza?
T cell response directed against “conserved” viral proteins
- CD4 T cells stimulate antibody responses
- CD8 T cell kill virally infected cells
Immunity generated against one strain may provide protection against another stratin (heterosubtypic immunity)
What is a cytokine storm?
- Also referred to tas systemic inflammatory response syndrom (SIRS)
- SIRS may explain the devastating nature of the 1918 strain of influenxa.
- The immune system overreacts towards teh pathogen
- Cytokines signal macrophages to travel to the site of infection, causing damage to the body and organ failure.
- H5N1 avian influenza virus also causes SIRS and is at least 50% lethal in humans
- See Virus File 12-2
Describe the properties of the Influenza A Viral Particles?
Properties of the Influenza A Particle
- Immediately after isolation, particles are filamentous
- After several passages in cell cultures, the particles become spherical
What is the Influenza Nomenclature?
- Influenza type (A or B)
- Species isolated form/(unless human)
- Place of isolation (geographic)
- Strain designation/Isolate number
- Year isolation
- HA and NA subtypes
What is HA and NA subtypes of Influenza A Viruses?
- 16 different HA subtypes
- 9 different NA subtypes
- Only H 1, 2 and 3, and N 1 and 2 are comomonly found in human
- H5, H7, and H9 occur rarely (bird transmitted viruses)
What is the Influenza Virus Genome?
Eight influenza virus genome segments (-ssRNA) code for a total of 11 different viral proteins
- Nine of the proteins are packaged into viral particles.
What are important parts of Influenza A Life cycle?
The low pH causes HA to undergo a conformational change
What is Viral Hemagglutinin?
Hemagglutinin (HA) protein binds to cell receptors and mediates fusion of the envelope with the endosomal membrane
- Heemagglutinin protein binds to sialic acid resdiues on muco-proteins
- HA can agglutinate red blood cells which is the basis for the hemagglutination assay
- HA is a type I transmembrane protein
What is involved in the uncoating step in Influenza A?
- M2 ion channel in the viral envelope allows H+ ions to penetrate the virion
- Weakens the viral M1 matrix protein from the viral RNA, NP and transcriptase complex (RNP)
- RNPs released into the cytoplasm
- Amantidine (sold as Symmetrel) and rimantidine (sold as Flumadine) block the M2 ion channel function, interfering with uncoating
What are viral Nucleocapsids?
Nucleocapsid protein (NP) binds to viral genome RNA
- NP protein wraps the RNA into an unususal twin helical conformation with a central loop
Trimer consisting of RNA polymerase proteins PA, PB1, and PB2 bound to 5’ and 3’ ends of RNA
- Contain nuclear localization signals that interact with importin-a to protmote entry into the nucleus
- Nucleocapsids enter the nucleus where mRNA synthesis and RNA replication occur.
What is involved in the Transport of Viral mRNAs and Proteins during replication?
Unlik other RNA viruses, orthomyxoviruses replicate in the nucleus.