LT 11 The Respiratory System Influenza virus

Question 1

Influenza virus

Answer 1

– Family: Orthomyxoviridae
– Four genera: Influenza A, B, C, D
– Only Influenza A (IAV) and Influenza B
(IBV) cause significant disease in humans
– IAV is also found in aquatic migrating
birds, poultry, pigs, horses, dogs, seals
and bats
– IBV is exclusively found in humans

– Enveloped virus
– Genome:
==> ssRNA
==> negative sense (3’ → 5’)
==> Segmented genome

Question 2

Front: What are the primary functions and features of the respiratory system in healthy and diseased states?

Answer 2

Functions: Gas exchange (O2 in, CO2 out), pH regulation, voice production, and protection against pathogens.
Healthy State: Efficient gas exchange, robust mucociliary clearance, and strong immune defenses.
Diseased State: Conditions like COPD, asthma, and infections can impair gas exchange, damage lung tissue, and disrupt homeostasis.

Question 3

Front: What are the resident microbes and antimicrobial defenses of the respiratory system?

Answer 3

Resident Microbes: Commensal bacteria like Streptococcus, Neisseria, and Haemophilus species.
Antimicrobial Defenses: Mucociliary escalator, alveolar macrophages, secretory IgA, lysozyme, and defensins.

Question 4

Front: Describe the diversity of Streptococcus, Mycobacteria, Aspergillus, and influenzavirus.

Answer 4

Streptococcus: Diverse group with species causing pharyngitis, pneumonia, and more (S. pyogenes and S. pneumoniae).
Mycobacteria: Includes M. tuberculosis, causing TB, with a waxy cell wall and slow growth.
Aspergillus: Fungal species like A. fumigatus, causing aspergillosis, particularly in immunocompromised individuals.
Influenzavirus: RNA viruses with high mutation rates, leading to seasonal flu variability and potential pandemic strains.

Question 4

Front: What are the major microbial insults to the respiratory system, their sources, and transmission methods?

Answer 4

Major Insults: Influenza, tuberculosis, pneumonia, bronchitis, and fungal infections.
Sources: Contaminated air, droplets from infected individuals, environmental fungi.
Transmission: Airborne droplets, direct contact, and environmental exposure.

Question 5

Front: What are the epidemiology, transmission, and pathology of S. pyogenes, M. tuberculosis, A. fumigatus, and influenzavirus infections?

Answer 5

Epidemiology: High global burden; M. tuberculosis and influenzavirus cause significant morbidity and mortality.
Transmission: S. pyogenes and influenzavirus spread through droplets; M. tuberculosis through airborne particles; A. fumigatus via spore inhalation.
Pathology:
S. pyogenes: Causes pharyngitis, scarlet fever.
M. tuberculosis: Causes granulomas in lungs.
A. fumigatus: Causes invasive aspergillosis.
Influenzavirus: Causes respiratory inflammation and systemic symptoms

Question 6

Front: What are the virulence mechanisms, host responses, and control measures for respiratory pathogens?

Answer 6

Virulence Mechanisms:
S. pyogenes: M protein, exotoxins.
M. tuberculosis: Mycolic acid, intracellular survival.
A. fumigatus: Gliotoxin, proteases.
Influenzavirus: Hemagglutinin and neuraminidase for entry/exit.
Host Response: Inflammation, antibody production, T-cell mediated immunity.
Control Measures: Vaccination, antibiotics (penicillin for S. pyogenes, rifampin for TB), antifungals, and antiviral drugs (oseltamivir for influenza).

Question 7

Front: How do the discussed microbes interact with the respiratory system, and what are the differences in transmission and spread?

Answer 7

Microbe-Respiratory System Relationships:
S. pyogenes colonizes the throat, can cause systemic infections.
M. tuberculosis infects alveoli, leading to granuloma formation.
A. fumigatus colonizes airways, especially in weakened hosts.
Influenzavirus: Infects respiratory epithelium, causing widespread inflammation.
Transmission and Spread: Airborne transmission common for all; differences in spread based on environmental stability and host factors.

Question 8

Front: What roles do the PA, PB1, and PB2 proteins play in the influenza virus?

Answer 8

PA, PB1, PB2: Subunits of the viral RNA polymerase.
Function: Involved in mRNA synthesis and genome replication (RNA-dependent RNA polymerase, RdRp).
Note: The polymerase complex is error-prone, leading to mutations that drive viral evolution.

Question 9

Front: What is the structure and genome composition of the influenza virus?

Answer 9

Structure: Enveloped virus with a lipid membrane.
Genome:
ssRNA (single-stranded RNA)
Negative sense (3’ → 5’)
Segmented genome: 8 RNA segments.

Question 10

Front: What are the functions of HA and NA in the influenza virus, and why are they important?

Answer 10

HA (Hemagglutinin): Facilitates viral entry by binding to sialic acid receptors on host cells.

NA (Neuraminidase): Enables viral exit by cleaving sialic acid, releasing new virions.
Importance: HA and NA are major targets for neutralizing antibodies and are key to vaccine design.

Question 11

Front: What are the roles of M1, M2, NP, and NS proteins in the influenza virus?

Answer 11

M1 (Matrix Protein): Involved in virus assembly and stability.
M2 (Membrane Protein): Functions as an ion channel, important for viral uncoating.
NP (Nucleocapsid Protein): Protects the viral RNA genome.
NS (Non-Structural Proteins): Inhibit host antiviral responses, including type I interferon (IFN) production.

Question 12

Front: How is the nomenclature of influenza A and B viruses determined?

Answer 12

Format: Type/Town/# of isolates/Year isolated/Major HA and NA subtype (for IAV).
Example: A/Switzerland/8060/2017 (H3N2).
Subtypes:
18 HA subtypes: Only H1, H2, H3 found in human IAV.
11 NA subtypes: Only N1, N2 found in human IAV.
Note: IAV tends to cause more severe infections; currently circulating strains include H3N2 and H1N1pdm09.

Question 13

Front: Describe the initial steps of the influenza virus lifecycle, including entry and uncoating.

Answer 13

Attachment: HA binds to sialic acid receptors on host cells.
Entry: Virus is endocytosed into the host cell.
Uncoating: Triggered by a pH drop in the endosome, which activates M2 ion channels, leading to the release of viral RNA into the cytoplasm.

Question 14

Front: How does the influenza virus replicate its genome and assemble new virions?

Answer 14

Genome Replication:
Negative-sense ssRNA is transcribed into positive-sense mRNA.
Positive-sense RNA serves as a template for synthesizing new viral RNA.
Assembly: Viral proteins and RNA are assembled into new virions at the host cell membrane.
Exit: NA facilitates the release of virions from the host cell by cleaving sialic acids.

Question 15

Front: What are the primary modes of influenza virus transmission?

Answer 15

Airborne: Via respiratory droplets and aerosols.
Fomite: Transmission through contaminated surfaces.
Direct Contact: Transmission through direct physical contact with an infected person.

Question 16

Front: What is the pathophysiology of influenza infection in the respiratory tract?

Answer 16

Infection: Virus infects epithelial cells of the respiratory tract.
Severity: Severity increases with replication in the lower respiratory tract, leading to severe inflammation.
Impact: Causes symptoms ranging from mild respiratory illness to severe pneumonia, especially in the lower airways.

Question 17

Front: Why are mutations and antigenic drift important in the context of influenza virus evolution?

Answer 17

Mutations: High mutation rates in viral RNA polymerase lead to frequent changes in the virus’s genetic makeup.
Antigenic Drift: Small mutations in HA and NA proteins allow the virus to evade host immunity, leading to seasonal flu outbreaks and requiring frequent updates to vaccines.

Question 18

Front: What are the key strategies for preventing and controlling influenza virus infections?

Answer 18

Vaccination: Annual flu vaccines targeting circulating strains.
Antiviral Medications: NA inhibitors (e.g., oseltamivir) can reduce the severity and duration of illness if administered early.
Public Health Measures: Hand hygiene, mask-wearing, and isolation of infected individuals to reduce transmission.

Question 19

Front: What is bird flu, and how is it currently affecting global health?

Answer 19

Current Outbreaks: Large outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in wild birds and poultry.
Transmission: Spread to other mammals has been observed.
Human Infections: Rare so far.
Geographical Spread: No cases of H5N1 in Australian birds, but found on every other continent.
Australia’s Experience: Previous outbreaks of HPAI H7N9, H7N3, and H7N9.

Question 20

Front: What are the main antiviral treatments for influenza, and how do they work?

Answer 20

Amantadine: Inhibits the M2 protein, blocking viral uncoating.
Zanamivir and Oseltamivir: Inhibit neuraminidase, preventing the release of new virions from infected cells.

Question 21

Front: What are the key characteristics of SARS-CoV-2, the virus responsible for COVID-19?

Answer 21

Virus Family: Member of the Coronaviridae family.
Genome: Single-stranded, positive-sense RNA, non-segmented.
Structure: Enveloped virus.

Question 22

Front: What are the types of influenza vaccines, and how are they administered?

Answer 22

Annual Vaccination: Necessary due to antigenic drift.
Types of Vaccines:
Killed Virus Vaccine: Administered intramuscularly.
Protein Subunit Vaccine: Administered intramuscularly.
Live Attenuated Vaccine: Administered intranasally, recommended for individuals aged 2-49 years who are at low risk.

Question 23

Front: What are the key structural components of the SARS-CoV-2 virion?

Answer 23

Spike (S) Protein: Glycosylated trimer with two subunits, S1 binds to ACE2 receptors, and S2 mediates membrane fusion.
N (Nucleocapsid) Protein: Binds viral RNA, forming the ribonucleoprotein complex.
M (Membrane) Protein: Organizes virion assembly.
E (Envelope) Protein: Involved in assembly and budding.
RNA Genome: Approximately 30 kb in length.

Question 24

Front: Describe the replication cycle of SARS-CoV-2.

Answer 24

1. Attachment and Entry: S1 binds to ACE2 receptors ( on host cell) , and the virus enters the cell.
2. Translation of Viral Genes: Host ribosomes translate viral RNA.
3. Genome Replication: Positive-sense RNA is replicated via a negative-sense RNA intermediate.
4. Virion Assembly: Proteins and RNA assemble into new virions.
5. Virion Release: New virions are released via exocytosis.

Question 25

Front: What is the pathogenesis of SARS-CoV-2 infection, including key clinical features?

Answer 25

Incubation Period: Mean interval between infection and symptom onset is 4-5 days.
Severe Cases: Can progress to acute respiratory distress syndrome (ARDS) 8-9 days after symptom onset.
Cytokine Storm: An overactive immune response can lead to multi-organ failure and death.

Question 26

Front: What are the primary modes of transmission for influenza?

Answer 26

Airborne: Via respiratory droplets and aerosols.
Fomite: Transmission through contaminated surfaces.
Contact: Direct physical contact with an infected person.

Question 27

Front: What are the primary strategies for preventing SARS-CoV-2 transmission?

Answer 27

Vaccination: Use of mRNA, vector, or inactivated vaccines.
Public Health Measures: Mask-wearing, hand hygiene, social distancing, and quarantine measures.

Question 27

Front: What are the major microbial insults to the respiratory system, and how do they impact morbidity and mortality?

Answer 27

Common Pathogens:
Bacteria: Streptococcus pneumoniae, Mycobacterium tuberculosis.
Viruses: Influenza virus, SARS-CoV-2.
Fungi: Aspergillus fumigatus.
Impact:
Morbidity: Leads to a range of respiratory illnesses from mild (e.g., common cold) to severe (e.g., pneumonia, tuberculosis).
Mortality: Significant global mortality, especially in vulnerable populations (e.g., influenza pandemics, COVID-19).
Sources:
Humans: Direct transmission via droplets/aerosols (e.g., influenza, COVID-19).
Animals: Zoonotic sources (e.g., avian influenza).
Environment: Fungal spores (e.g., Aspergillus).

Question 28

Front: How does the diversity of the influenza virus contribute to the evolution of seasonal flu and the emergence of pandemic flu?

Answer 28

Types:
Influenza A: Causes most pandemics, infects humans, birds, and other animals.
Influenza B: Primarily infects humans, less genetically diverse than A.
Influenza C: Mild infections, less common.
Evolution:
Antigenic Drift: Small mutations in HA and NA genes cause seasonal flu variations.
Antigenic Shift: Reassortment of RNA segments between different strains leads to pandemics (e.g., H1N1 in 2009).
Pandemic Emergence:
Caused by novel influenza A subtypes with little pre-existing immunity in humans (e.g., H5N1, H7N9).

Question 29

Front: Describe the epidemiology and transmission of the influenza virus.

Answer 29

Epidemiology:
Seasonality: Peaks in winter months in temperate regions.
Pandemics: Occur irregularly; notable pandemics include 1918 H1N1, 2009 H1N1.
Transmission:
Airborne Droplets: Primary mode of transmission.
Fomites: Contaminated surfaces.
Direct Contact: Person-to-person spread through touch.

Question 30

Front: What are the key pathological features and virulence mechanisms of the influenza virus?

Answer 30

Pathology:
Infects respiratory epithelial cells, leading to cell death and inflammation.
Severe cases involve lower respiratory tract infection, leading to pneumonia.
Virulence Mechanisms:
HA Protein: Binds to sialic acid receptors on host cells, initiating infection.
NA Protein: Cleaves sialic acid, facilitating viral release.
NS1 Protein: Inhibits host immune responses (e.g., interferon production).

Question 31

Front: How does the host immune system respond to influenza virus infection?

Answer 31

Back:

Innate Immunity:
Recognition of viral RNA by pattern recognition receptors (e.g., RIG-I).
Production of interferons and cytokines to limit viral replication.
Adaptive Immunity:
Humoral Response: Production of neutralizing antibodies against HA and NA.
Cellular Response: Cytotoxic T cells target infected cells.
Immune Evasion: Influenza virus mutations can lead to immune escape, reducing vaccine effectiveness.

Question 32

Front: What are the methods for diagnosing, treating, and controlling influenza virus infections?

Answer 32

Back:

Diagnosis:
RT-PCR: Detects viral RNA in respiratory samples.
Rapid Antigen Tests: Detects viral proteins, less sensitive.
Treatment:
Antivirals: Oseltamivir, Zanamivir (NA inhibitors).
Supportive Care: Hydration, antipyretics.
Control:
Vaccination: Annual flu vaccine based on predicted strains.
Public Health Measures: Quarantine, mask-wearing, hand hygiene.

Question 33

Front: How do the infections discussed compare in terms of transmission, spread, and impact on the respiratory system?

Answer 33

Influenza vs. COVID-19:
Transmission: Both primarily spread through droplets/aerosols, but SARS-CoV-2 has a higher transmission rate.
Impact: Both can cause severe respiratory illness, but SARS-CoV-2 has broader systemic impacts.
Bacterial vs. Viral Infections:
Bacteria: (e.g., Streptococcus pneumoniae) often cause localized infections like pneumonia.
Viruses: (e.g., Influenza, SARS-CoV-2) can cause widespread respiratory involvement and systemic symptoms.
Fungal Infections:
(e.g., Aspergillus fumigatus) generally affect immunocompromised individuals, causing invasive lung disease.