Respiratory Viruses I: Infuenza Viruses Flashcards
The Major Viral Agents of ARD (8):
- Influenza
- Parainfluenza
- RSV
- Metapneumovirus
- Adneovirus
- Rhinovirus
- Coronavirus
- Bocavirus
Type A
- Humans
- Swine
- Birds
- Horses
- Seals
Type B
- Humans
- Seals
Type C
- Humans
- Swine
Structure of Influenza A
- 8 segments of single stranded (-) RNA
- Nucleoprotein covers (coats) RNA to form ribonucleoprotein complex
- M (matrix) surrounds ribonucleoprotein
- Envelope contains H (hemagglutinin) and N (neuraminidase) glycoprotein spikes
Influenza [] undergoes more significant antigenic changes than [] and [].
Influenza A undergoes more significant antigenic changes than B and C.
Genetic changes in Infuenza A occur due to:
- Antigenic drift and shift of both H or HA and N or NA glycoproteins due to mutation and recombination (reassortment), respectively
- Drastic changes in pandemics
Antigenic Drift
Antigenic Shift
How many types of H in Influenza A?
Three types of H (H1, H2 and H3)
How mant types of N in Influenza A?
Two types of N (N1 and N2)
Influenza Replication
i. Adsorption mediated by H by interacting with the receptor (sialic acid glycoprotein.
ii. N promotes smooth passage of the virus in the respiratory tract and later in viral release from infected cells.
iii. Uncoating in the cytoplasm to release viral genome.
iv. Only (-) RNA virus that replicates in the nucleus.
v. RNA segments migrate to nucleus to prime its transcription, uses host RNA primers, transcription/replication performed by viral RNA dependent RNA polymerase.
vi. Nucleocapsid assembled in the nucleus. vii. Buds through plasma membranes at sites where H and N spikes are expressed and M (matrix) protein has accumulated.
Where does Influenza replicate?
Only ( - ) RNA to replicate in the nucleus.
RNA segments migrate to nucleus to prime its transcription, uses [] RNA primers, transcription/replication performed by [] RNA dependent RNA polymerase.
RNA segments migrate to nucleus to prime its transcription, uses host RNA primers, transcription/replication performed by viral RNA dependent RNA polymerase.
Where is the Influenza nucleocaspid assembled?
Nucleocapsid assembled in the nucleus.
How is Influenza transmitted?
Transmission is direct, by infective droplet nuclei, or indirect, by hand transfer of contaminated secretions.
Where does Influenza replicate?
Ciliated epithelial cells in respiratory tract.
How does Influenza damage host?
- Functional and structural ciliary abnormalities due to viral replication in ciliated epithelial cells
- Shut off of host protein and nucleic acid synthesis
- Release of lysosomal enzymes and desquamation of ciliated and mucus-producing cells
- Chemotactic stimulus and pro-inflammatory cytokines cause major inflammation
- Damage renders host susceptible to invasive bacterial superinfection
Influenza Immunity
- Cell mediated & humoral immunity control infection
- Antibody to H is most protective
Influenza Incubation
1-2 days
Influenza Symptoms
- Abrupt onset leading to rapid development of symptoms including fever, myalgia, headache, muscle ache, chills, cough and fatigue.
- Improvement in 5-7 days, followed by prolonged cough, fatigue (2 to several weeks)
Progressive Infection can lead to:
- Progressive infection can cause viral pneumonia
- Damage caused by viral replication and acute inflammatory response render the host highly susceptible to invasive bacterial superinfection.
Most common secondary bacterial infection agents:
- Secondary bacterial infection causing pneumonia (Streptococcus pneumonia, Haemophilus influenzae, Staphylococcus aureus).
- Predisposing factors: age, heart, and lung defects
Complications from Influenza:
- Reye’s syndrome: severe fatty infiltration of the liver and cerebral edema, 2 to 12 days
- Guillain-Barre syndrome: Muscle weakness leading to paralysis
Influenza Diagnosis
•: Clinical picture, isolate virus in cell culture and serology (antibody titer to H), rapid antigen and RT-PCR
Influenza Treatment
•Neuraminidase inhibitors
- Oseltamivir (Tamiflu) - oral
- Zanamivir (Relenza) – inhalation
- Peramivir (Rapivab) – injectable , not for prophylaxis
- Baloxavir (Xfluza) – oral
- Active against influenza A and B viruses
Influenza Prevention
- The Flu Shot - inactivated vaccine (killed virus)
- The Nasal Spray Flu vaccine (live attenuated flu vaccine or FluMist)
Human influenza viruses vs, Avian influenza viruses
H5N1 Avian Flu Clinical Disease
H1N1 Swine Flu
- Greater disease burden in people younger than 25 years of age than older people
- 70% of the hospitalized people have had one or more underlying conditions; pregnancy, diabetes, heart disease, asthma and kidney disease
- High fatality in younger infected population
H1N1 Swine Flu Symptoms
•Replication of H1N1 swine virus destroys lungs alveoli often causing acute respiratory distress syndrome, viral pneumonia in the absence of bacterial super infection
Cytokine Storm
A severe immune reaction in which the body releases too many cytokines into the blood too quickly.
H1N1 Swine Flu Diagnosis
- Clinical
- Rapid influenza test (antigen), 40-69% sensitivity
- Real time RT-PCR
H1N1 Swine Flu Treatment
•Neuraminidase inhibitors: Oseltamivir (Tamiflu) and Zanamivir (Relenza)
H1N1 Swine Flu Prevention
- Preventive measures
- H1N1 was included with seasonal flu vaccine since 2010 and onwards
[] is dominant on epithelial cells of nasal mucosa, paranasal sinuses, pharynx, trachea and bronchi, whereas [] is found on non- ciliated bronchiolar cells at the junction between respiratory bronchiole and alveolus.
SAα2,6Gal is dominant on epithelial cells of nasal mucosa, paranasal sinuses, pharynx, trachea and bronchi, whereas SAα2,3Gal is found on non- ciliated bronchiolar cells at the junction between respiratory bronchiole and alveolus
H5N1 Avian Flu Tropism and Pathogenesis
H5N1 was not easily transmitted because its receptor, SAα2,3Gal, is found in lower respiratory tract.
H1N1 Swine Flu Tropism and Pathogenesis
H1N1 swine 2009 infected cells of upper respiratory tract by interacting with SAα2,6Gal and deep in the lungs with SAα2,3Gal compared with human influenza that interacts only with SAα2,6Gal in upper respiratory tract.
Requirements for Influenza Pandemic
- A new human influenza A subtype
- Causes serious illness
- Spreads easily from human-to-human
- The first two prerequisites were met for H5N1, but not the last
- However, all 3 prerequisites were met for H1N1 swine origin
- Each new human infection is an opportunity for the virus to change
