Respiratory Tract Infections

In host cells viruses cause

Tissue damage and Inflammation

Examples of physcial manifestations of viral infections

Pharyngitis

Hepititis

Pharyngitis is the

inflammation/ulceration of the tonsillar/pharyngeal tissue

Hepititis is

inflammation of the liver, progressing to cirrhosis/carinoma

Immunosuppressants can

reduce an exaggerated inflammatory response

Immunosuppressants reduce repsonse by

Reduction anibody productions

inhibit production of immune cells

Block chemical messengers

Lysogenic Viruses

are non-virulent and do not cause disease

Lytic Viruses

are virulent and cause disease

Step 1 of a bacteriophage life cycle - virulent/non-virulent

Attachment and injection - The phage attaches to the host bacterial cell and injects its double-stranded DNA into the cell.

Step 2 of a bacteriophage life cycle - virulent/non-virulent

Circularization and decision point The injected phage DNA circularizes. At this point, the virus "chooses" one of two paths: the lytic cycle or the lysogenic cycle.

Step 3A - bacteriophage life cycle - virulent

Synthesis and assembly New phage DNA and proteins are synthesized using the host cell's machinery, then assembled into complete virus particles (virions).

Step 4A - bacteriophage life cycle - virulent

Lysis and release The host cell bursts (lyses), releasing the newly formed phage virions to infect other cells.

Step 3B - bacteriophage life cycle - non-virulent

Integration The phage DNA integrates into the bacterial chromosome by recombination, becoming a prophage.

Step 4B - bacteriophage life cycle - non-virulent

Normal reproduction The lysogenic bacterium reproduces normally, copying the prophage along with its own DNA through many cell divisions.

Step 5B - bacteriophage life cycle - non-virulent

Excision (occasionally) Occasionally, the prophage excises itself from the bacterial chromosome by another recombination event, initiating the lytic cycle and starting the process over.

Step 1 - General Viral Reproductive Cycle

Attachment The virus (a capsid enclosing its DNA) binds to the surface of the host cell.

Step 2 - General Viral Reproductive Cycle

Entry and uncoating The virus enters the cell and its DNA is released (uncoated) from the capsid.

Step 3 - General Viral Reproductive Cycle

Replication The viral DNA is replicated, producing multiple copies of the viral genome.

Step 4 - General Viral Reproductive Cycle

Transcription The viral DNA is transcribed into mRNA.

Step 5 - General Viral Reproductive Cycle

Translation of viral proteins The mRNA is translated to produce capsid proteins (and other viral components).

Step 6 - General Viral Reproductive Cycle

Self-assembly and exit New virus particles self-assemble from the viral DNA and capsid proteins, then exit the cell (typically by budding or lysis) to infect new host cells.

Fomite is

an inanimate object that can transmit infection between people

Myeloperoxidase - found in neutrophils

makes mucus green due to increase neutrophil numbers during infection

Croup

Childhood infection causing swelling inside trachea

Otitis media

Inflammation of the middle ear

How many transmission modes are there?

Three: direct, aerosol, indirect

Direct transmission

Contact with infected person

Aerosol transmission

Inhalation of infected droplets

Indirect transmission

contact with infected fluids on surfaces/objects

The most common cause of the common cold are

Rhinoviruses ~40%

Rhinoviruses have how many virus types

100 distinct types

The common cold is caused by how many specific types

~200 specific viruses

Other major causes of the cold

Coronavirus

adenovirus

respiratory synytial virus (RSV)

Symptoms of the common cold

runny/stuffy nose

sneezing

sore throat

cough

cogestion

mild body aches/headache

fever is rare and mild

Common colds are typically

upper respiratory tract infections

Influenza is caused by

Type A, B and C viruses

Flu symptoms eppear

Quickly and severly

Flu symptoms

Runny/stuff nose, sneezing, sore throat, cough, muscle aches, fatigue, usually high fever

Flu can affect

upper and lower respiratory tract

Mucus functions

Lubricates, protects (antimicrobial), and blocks (prevents spread of infections)

Viruses cause what percent of RTI

70%

Upper Respiratory Tract

Nose

Sinuses

Throat

Lower Respiratory Tract

Airways and lungs

LRTI’s

Influenza, croup, bronchiolitis, pneumonia

URTI’s

Connon cold, infulenza

URT viruses

Rhinovirus, Coronavirus, Influenza Virus, RSV, parainfluenza virus, herpes virus, adenovirus, boca virus, coxsackievirus

LRT

Influenza Virus, Parainfluenza Virus, RSV, Adenovirus, Bocavirus, MEtapneumovirus

Rhinitis is

Inflamation of the mucus membrane of the nose

Allergic Rhinitis is

caused by an allergen (seasonal/year round)

Viral non-allergic rhinitis

caused by rhinoviruses, coronavirus, adenovirus, RSV

Viral rhinitis treatment

No specific tratment required

Coricosteroid nasal spray - anti-inflammatory

Deongestant nasal spray - reduce swelling of nasal blood vessels

Allergic rhinitis treatment

Anti-histamine compound

Pharyngitis

erythema (redness) of the oropharynx, with or without tonsillar inflammation.

Tonsils

pair of soft tissue masses at the rear of the pharynx

Laryngitis

hoarse or gravelly voice (inflamed vocal cords altering airflow).

Laryngitis Viruses

Rhinovirus, parainfluenza, RSV, adenovirus

Pharyngitis and Tonsilitis are

commonly viral (70-80%)

Bacterial Pharyngitis and Tonsilitis are caused by

20–30% caused by group A beta-haemolytic streptococcus.

How many LRTI’s are there?

Four

Tracheitis is

Inflamation of the trachea

Bronchitis is

Inflamation of the bronchus

Bronchiolitis is

Inflamation of the bronchioles

Pneumonia is

Inflamation of the alveoli

Pnemonia cause

The air sacs (alveoli) become inflamed and fill with fluid instead of air, making breathing difficult; the lungs may not get enough oxygen. 

Typical Pneumonia viruses in adults

Influenza A and B

Typical pneumonia virus in children

RSV

Pneumonia complications

Respiratory failure – low oxygen / high carbon dioxide in the lungs. 

Sepsis – overwhelming inflammatory response → multiple organ failure, life-threatening. 

Pleural effusion – fluid builds up around the lung. 

Influenza Viruses Family

Orthomyxoviridae

Types of Influenza Viruses

A & B – cause seasonal flu epidemics each year. 

C – mild respiratory illness, not thought to cause epidemics. 

D – primarily affects cattle; not known to infect humans. 

All influenza viruses are

envloped viruses with segmented RNA

Influenza A and B have

8 RNA segemnts and 2 types of surface proteins

Influenza C has

7 RNA segments and 1 type of surface proteins

Type A target species

Birds, swine, humans, seals, horses

Type B

Humans

Type C

Humans and swine

Influenza A and B surface protiens

Spikes of glycoproteins: Haemagglutinin (HA, ~80%) and Neuraminidase (NA, ~20%) — targets for the host immune response.

HA (H1–H18) – role in viral attachment to host cells.

NA (N1–N11) – role in release of new virus particles by budding.

Surface proteins determine the subtype (e.g., H1N1, H3N2).

Influenza C surface proteins

Hemagglutinin-esterase-fusion, HEF

Pathogenesis of Influenza A Virus

1. Transmission and Entry

2. Attachment and Cell Entry

3. Replication

4. Cell damage and Tissue Injury

5. Immune Response and Cytokine Storm

6. Systemic Effects and Complications

7. Immune Evasion

Step 1 - Pathogenesis of IAV

Transmission and Entry: Spreads via aerosol droplets and fomites (contaminated surfaces).

Enters through the respiratory tract, targeting epithelial cells of the airways (trachea, bronchi, and bronchioles).

Step 2 - Pathogenesis of IAV

Attachment and Cell Entry

The viral hemagglutinin (HA) protein binds to sialic acid receptors on the host cell surface.

The virus is taken up by receptor-mediated endocytosis.

The low pH inside the endosome triggers a conformational change in HA, causing fusion of the viral envelope with the endosomal membrane.

The viral RNA is released into the cytoplasm.

Step 3 - Pathogenesis of IAV

Replication

The viral RNA is transported to the nucleus, where it is transcribed and replicated by the viral RNA-dependent RNA polymerase.

The neuraminidase (NA) protein later cleaves sialic acid, allowing newly formed virions to bud off and release from the cell.

Step 4 - Pathogenesis of IAV

Cell Damage and Tissue Injury

Infection causes necrosis and apoptosis of epithelial cells, stripping the ciliated airway lining.

This impairs mucus clearance and exposes the basement membrane, leading to inflammation and secondary bacterial infections.

Step 5 - Pathogenesis of IAV

Immune Response and Cytokine Storm

Infected cells release cytokines and chemokines, recruiting neutrophils, macrophages, and lymphocytes.

In severe cases, an excessive response causes a "cytokine storm" — high levels of TNF-α, IL-6, and interferons — leading to widespread tissue damage.

Cytotoxic T cells (CD8+) kill infected cells, contributing to both viral clearance and tissue pathology.

Step 6 - Pathogenesis of IAV

Systemic Effects and Complications

Local damage plus inflammatory mediators cause fever, myalgia, and malaise.

Complications include:

Primary viral pneumonia

Secondary bacterial pneumonia (e.g., Streptococcus pneumoniae, S. aureus)

Acute respiratory distress syndrome (ARDS)

Exacerbation of asthma/COPD, and in rare cases myocarditis or encephalitis

Step 7 - Pathogenesis of IAV

Immune Evasion

Antigenic drift (small mutations in HA/NA) allows the virus to evade pre-existing immunity.

Antigenic shift (reassortment of genome segments between strains) can create novel viruses with pandemic potential.

Antigenic drift

1. accumulation of mutations in the genes that code for regions on HA and NA ​

2. the virus becomes unrecognisable in the host due to changes in surface proteins​

3. leads to an infection and successful transmission since it is a new strain

Antigenic drift is a

slow, gradual, frquent process

Antigentic Drift can

cause an epidemic

Influenza A, B and C undergo

Antigenic drift

Antigenic Shift

1. intermixing of two or more viral genomes inside the host cell​

2. a new combination of genes​

3. a novel subtype of the virus​

4. not recognized by the host genome

Only inflenza A undgergoes

Antigenic shift

Antigenic shift is

a rare, sudden process

Antigenic shift can cause

a pandemic

Pandemic

Across international boarders

Epidemic

Contained within an area

Antigenic shift can jump

from one species to another

Examples of antigenic shift

Spanish flu (H1N1), Hong Kong flu (H3N2, 1968 pandemic)

Examples of Antigenic Drift

outbreaks of H3N2.

Influenza B has

two evolutionary lineages

Influenza B is more

antigenically stable than influenza A