LT 11 The Respiratory System Influenza virus Flashcards
Influenza virus
– 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
Front: What are the primary functions and features of the respiratory system in healthy and diseased states?
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.
Front: What are the resident microbes and antimicrobial defenses of the respiratory system?
Resident Microbes: Commensal bacteria like Streptococcus, Neisseria, and Haemophilus species.
Antimicrobial Defenses: Mucociliary escalator, alveolar macrophages, secretory IgA, lysozyme, and defensins.
Front: Describe the diversity of Streptococcus, Mycobacteria, Aspergillus, and influenzavirus.
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.
Front: What are the major microbial insults to the respiratory system, their sources, and transmission methods?
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.
Front: What are the epidemiology, transmission, and pathology of S. pyogenes, M. tuberculosis, A. fumigatus, and influenzavirus infections?
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
Front: What are the virulence mechanisms, host responses, and control measures for respiratory pathogens?
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).
Front: How do the discussed microbes interact with the respiratory system, and what are the differences in transmission and spread?
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.
Front: What roles do the PA, PB1, and PB2 proteins play in the influenza virus?
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.
Front: What is the structure and genome composition of the influenza virus?
Structure: Enveloped virus with a lipid membrane.
Genome:
ssRNA (single-stranded RNA)
Negative sense (3’ → 5’)
Segmented genome: 8 RNA segments.
Front: What are the functions of HA and NA in the influenza virus, and why are they important?
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.
Front: What are the roles of M1, M2, NP, and NS proteins in the influenza virus?
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.
Front: How is the nomenclature of influenza A and B viruses determined?
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.
Front: Describe the initial steps of the influenza virus lifecycle, including entry and uncoating.
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.
Front: How does the influenza virus replicate its genome and assemble new virions?
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.
Front: What are the primary modes of influenza virus transmission?
Airborne: Via respiratory droplets and aerosols.
Fomite: Transmission through contaminated surfaces.
Direct Contact: Transmission through direct physical contact with an infected person.
Front: What is the pathophysiology of influenza infection in the respiratory tract?
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.
Front: Why are mutations and antigenic drift important in the context of influenza virus evolution?
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.
Front: What are the key strategies for preventing and controlling influenza virus infections?
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.
Front: What is bird flu, and how is it currently affecting global health?
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.
Front: What are the main antiviral treatments for influenza, and how do they work?
Amantadine: Inhibits the M2 protein, blocking viral uncoating.
Zanamivir and Oseltamivir: Inhibit neuraminidase, preventing the release of new virions from infected cells.
Front: What are the key characteristics of SARS-CoV-2, the virus responsible for COVID-19?
Virus Family: Member of the Coronaviridae family.
Genome: Single-stranded, positive-sense RNA, non-segmented.
Structure: Enveloped virus.
Front: What are the types of influenza vaccines, and how are they administered?
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.
Front: What are the key structural components of the SARS-CoV-2 virion?
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.
