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.