The evolving risks of COVID-19 and other respiratory viruses
Page 1
Date: 18th March 2025
Presenter: Dr. David Courtney
Topic: The evolving risks of COVID-19 and other respiratory viruses
Affiliation: Queen's University Belfast, Wellcome-Wolfson Institute for Experimental Medicine
Page 2: Learning Outcomes
Understand the replication cycle of SARS-CoV-2.
Define the sites in the body where SARS-CoV-2 can infect and replicate.
Recognize the implications of oral transmission routes of respiratory viruses in clinical settings.
Page 3: Genetic Information Flow - not inpot
DNA: Genetic blueprint of organisms.
Central dogma of molecular biology: DNA → RNA → Protein
Key components:
Nucleobases: Building blocks of DNA and RNA.
Proteins: Functional molecules derived from genetic material.
Page 4: Genetic Material -not inport
Genes are encoded within DNA located in the nucleus.
DNA is transcribed into mRNA, which is transported to the cytoplasm.
In the cytoplasm, mRNA is translated into proteins by ribosomes.
Page 5: Baltimore Classification of Viruses - not import
GENETIC METERIAL PRESENT IN THE VIRION
Group I: dsDNA viruses
Group II: ssDNA viruses
Group III: dsRNA viruses
Group IV: ssRNA (+) viruses
Group V: ssRNA (-) viruses
Group VI: retroviruses (e.g., reverse transcription mechanisms)
Group VII: dsDNA viruses that replicate through an RNA intermediate.
Page 6: Definition of a Virus
Definition: Infectious, obligate intracellular parasites composed of genetic material (DNA or RNA) enveloped by a protein coat.
Examples: SARS-CoV-2, Tobacco Mosaic Virus, T4 bacteriophage.
Page 7: Common Respiratory Viruses
SARS-CoV-2 & other coronaviruses
Influenza viruses
Respiratory syncytial virus (RSV)
Rhinovirus
Adenoviruses
Page 8: Coronaviruses Overview
Characteristics: ssRNA viruses with an enveloped structure and pleomorphic morphology.
Common serogroups: 229E, NL63, OC43, HKU1, MERS, SARS-CoV, SARS-CoV-2. (virus with the same antigen
Seasonal infections, peaking in winter months.
Page 9: Influenza Virus Overview
RNA virus with a genome of 8 segments.
Enveloped with haemagglutinin and neuraminidase spikes.
Types: A, B, and C. Type A undergoes antigenic shift and drift.
Causes mild febrile illness; severe complications may arise such as pneumonia.
Page 10: Respiratory Syncytial Virus (RSV)
ssRNA enveloped virus from the Paramyxovirus family.
Strain variation; classified into subgroups A and B.
Common cause of severe lower respiratory tract disease in infants.
Responsible for 50-90% of bronchiolitis cases.
Page 11: Rhinovirus Overview
ssRNA viruses belonging to the picornavirus family.
Over 100 serotypes recognized.
infect upper respiratory tract
Major cause of common colds (30-50% of cases).
Page 12: Adenoviruses Overview
dsDNA virus, non-enveloped, with at least 47 known serotypes.
Causes a range of diseases: pharyngitis, pneumonia, conjunctivitis, gastroenteritis.
Page 13: SARS-CoV-2 Replication Cycle
Stages of viral replication: FOR GENERAL
Attachment: The virus binds to specific receptors on the host cell.
Entry/Uncoating: The virus enters the cell and releases its genetic material (DNA or RNA).
Transcription: The viral genome is transcribed into mRNA (Cov not needed).
Translation: The host ribosomes translate the viral mRNA into viral proteins.
Replication: The viral genome is copied to create more viral genetic material.
Assembly: New viral particles are formed from the replicated genome and proteins.
Release: The new viruses leave the host cell by lysis (cell bursts) or budding.
FOR COVID SPECIFICALLY
Attachment & Entry
The spike (S) protein of the virus binds to the ACE2 receptor on human cells.
The virus enters the cell via endocytosis or direct membrane fusion.
Uncoating
The viral envelope fuses with the host membrane.
This releases the positive-sense single-stranded RNA (ssRNA+) genome into the cytoplasm.
Primary Translation
SARS-CoV-2 is a positive-sense RNA virus, so its RNA can directly act as mRNA.
Host ribosomes translate the viral RNA into viral proteins.
The first proteins produced are non-structural proteins (NSPs), including RNA-dependent RNA polymerase (RdRP).
Transcription & Replication
RdRP transcribes the genome into subgenomic mRNAs to produce structural proteins.
NSPs also include proofreading enzymes that increase replication fidelity.
RdRP replicates the full-length genome to produce new copies of viral RNA.
Secondary Translation & Assembly
Structural proteins (spike, envelope, membrane, and nucleocapsid) are synthesized.
Viral components are assembled in the endoplasmic reticulum (ER) and Golgi apparatus.
Fully formed virions are packaged within vesicles.
Exocytosis (Release)
The newly formed viruses are transported in vesicles to the cell membrane.
They are released via exocytosis, ready to infect new cells.
Page 20: Innate Immunity from host - IFN Induction
Type I IFN system (IFNα/β) plays a critical role in antiviral defense.
Secreted upon viral infection to induce antiviral mechanisms.
(not important)
Viral Detection: PRRs (RIG-I, MDA5, TLRs) detect viral RNA/DNA.
Signaling: Activates IRF3/7, NF-κB, triggering IFN gene transcription.
IFN Production: Type I (IFN-α, IFN-β) and Type III (IFN-λ) are released.
JAK-STAT Activation: IFNs bind receptors, triggering ISG production.
Antiviral Effects: ISGs inhibit viral replication and boost immunity.
SARS-CoV-2 and other viruses suppress IFN induction to evade immunity
Page 21: Adaptive Immunity - Antibodies
Initial IgM response followed by a sustained IgG response.
Structure:
Antigen binding (Fab) regions and receptor binding (Fc) regions.
Antibodies functionally neutralize viruses.
Page 22: Neutralising Antibodies in Adaptive Immunity
IgA primarily found at mucosal surfaces.
Antibodies act by:
Blocking attachment
Blocking endocytosis
Neutralizing after replication
Aggregation of viruses
Page 23: Importance of Replication Site
Understanding replication sites aids:
Targeting therapeutics
Studying virus spread
Informing clinical dynamics of infections
Page 24: Lower Respiratory Tract Replication
SARS-CoV replicates readily in ACE2 expressing cells, limiting spread before symptoms. ???
SARS-CoV-2 also replicates in the lower respiratory tract, resulting in severe disease and upper airway shedding.
Page 25: Upper Respiratory Tract Dynamics
Unique to SARS-CoV-2: active shedding from upper respiratory epithelia occurs when symptoms are mild.
Significant implications for population transmission dynamics.
Page 26: Transmission Mechanics
Respiratory viruses transmitted through upper and lower respiratory tracts.
Mechanisms include retching, coughing, sneezing, and speaking.
Page 27: Particle Size in Aerosol Transmission
Importance of particle size:
Aerosol transmission can persist for hours.
Various diameters affect residence time and deposition efficiency (where they end up) in different regions of the respiratory tract.
Larger particles settle quickly (shorter time)
Smaller particles may stay longer (more time to deposit or be exhaled)
Page 28: Factors Affecting Aerosol Transmission
Stability of common respiratory viruses affected by:
Temperature - more stable in lower temps
Humidity specifics - flu favouring low humidity
UV radiation - inactive virus
Importance of airflow, ventilation, and filtration
Page 29: Breathing in Clinical Settings
Patients often found in confined spaces with minimal ventilation.
Air filtration needs (HEPA filters) to remove viral particles are critical.
Page 30: Aerosolization in Clinical Procedures
Dental devices contributing to aerosols:
Ultrasonic scalers, air polishing, air-water syringes, air-turbine preparation, air abrasion.
Page 31: Minimizing Airborne Contamination
Suggested methods:
Barrier protection (masks, gloves, eye protection)
Pre-procedural rinse
High-efficiency air filters and UV treatment of ventilation systems
Page 32: Summary
SARS-CoV-2 replicates predominantly in the respiratory tract.
Upper airway replication primarily facilitates spread; lower airway replication leads to severe disease.
Antibodies, especially IgA, provide defense against viral infection.
Clinical practices can heighten the spread of respiratory viruses, necessitating stringent precautions.