Infectious Diseases Week 7

How are respiratory pathogens transmitted person-to-person

via aerosol droplets

do large droplets fall quickly or slowly

fall quickly

What happens to moderate/small droplets

they persist as microdroplets that remain in air for longer

do most pathogens survive well in the air

no they survive poorly, only survive short distances

what does the environmental niche favour

diff. microorganisms

What major respiratory pathogens are covered in HLTH3250

Mycobacterium tuberculosis

Coronavirus

Influenza virus

what is the classification of viruses

Obligate intracellular parasites

the smallest and simplest life form on earth that can only replicate in living susceptible cells

What changes do viruses cause to cells

Changes to antigenicity, metabolism, and viral particle production

What leads to the manifestations of viral disease

The host response to cell death and viral presence

Are viruses motile

No. They are non-motile and depend on external physical factors to infect other susceptible cells

What percentage of human DNA is made up of ancient retroviral genomes

Approximately 8%

What is viremia

The presence of viral particles in the blood

What is tropism

The ability of a virus to infect a certain tissue and replicate there

What factors does tropism depend on

Accessibility of the target cell

susceptibility (presence of relevant receptor)

permissiveness of the target cell (host cell relevant factors for replication)

avoidance of innate and adaptive immunity

How are viruses classified by genome

DNA genome vs RNA genome

positive or negative orientation

single or double stranded

linear, circular or segmented

What does positive (+) orientation mean in viral RNA

The RNA can directly function as mRNA and be translated by host ribosomes

What does negative (-) orientation mean in viral RNA

The RNA must be converted to positive sense before translation

what is the genome size of a human

~ 25000 genes

what is the genome size of e.coli

~ 2000 genes

what is the genome size of viruses

~ 400 genes

what is a naked virus

Viruses with a capsid only

what is an enveloped virus

Viruses with an envelope

What are the two routes for viral entry

Endocytic route (clathrin-mediated endocytosis and penetration)

non-endocytic route (fusion at the cell surface)

What are the six steps of the viral life cycle

1. Attachment

2. Penetration

3. Uncoating

4. Biosynthesis

5. Assembly

6. Release

What happens during attachment

The virus becomes attached to a target epithelial cell

What happens during penetration

The cell engulfs the virus by endocytosis

What happens during uncoating

Viral contents are released

What happens during biosynthesis

Viral RNA enters the nucleus, where it is replicated by the viral RNA polymerase

What happens during assembly

New phage particles are assembled

What happens during release

New viral particles are made and released into the extracellular fluid. The cell is not killed in the process and continues to make new virus

Where do respiratory viruse pathogens mainly enter

via the nasal passage

where do respiratory viral pathogens mainly replicate

in nasopharyngeal epithelial cells, and the lower respiratory tract (LRT)

How do respiratory viruses alter cellular homeostasis (4 things)

Direct lysis of infected cells

inducing apoptosis

creating inclusion bodies

syncytia formation (fusing of infected cells into large multi-nucleated cells)

How may respiratory viruses act at a distance

Through neuronal pathways

What nervous supplies may be affected by respiratory viruses

Parasympathetic, sympathetic, and non-adrenergic, non-cholinergic nervous supply

What is the sequence of respiratory virus pathogenesis

1. Entry

2. Replication

3. Inflammatory mediators (chemokines, cytokines, bradykinins) released

4. Immune response (virus eradication) or Vascular leakage + glandular secretion (symptoms: rhinorrhoea, cough, sneezing)

What is measles

An acute, highly infectious disease that often affects susceptible children

What virus causes measles

Paramyxovirus – a negative-strand SSRNA virus

What are the main immune cell targets of measles

T-cells, B-cells, macrophages, and DCs expressing CD150 (SLAM

What is Nectin-4 and where is it found

A receptor on epithelial cells – part of the adherens junction complex on the basolateral side, under tight junctions. Also on keratinocytes and endothelial cells

What may Nectin-4 play a role in

The characteristic skin rash of measles

What is the treatment for measles

No antiviral therapies

Supportive care: antipyretics, antitussives, hydration and/or envivo controls (humidification)

What is the receptor for measles on immune cells

SLAM (CD150)

What is the receptor for measles on epithelial cells

Nectin-4

what does the Varicella-Zoster virus cause

Varicella pneumonia occurs 1 – 6 days after rash

what are symptoms of varicella pneumonia

tachypnoea, chest-tightness, cough, dyspnoea, fever

What does Varicella-Zoster virus establish in neurons

Life-long, latent infection in neurons

What happens when VZV reactivates

It migrates to the skin surface – causing shingles

How is VZV transmitted

Direct contact, aerosol inhalation of vesicular fluid from skin lesions, and possibly respiratory secretions

What do VZV lung lesions look like

Multiple small, round calcific lung lesions

Who is vulnerable to VZV

Immunocompromised and unvaccinated individuals

What is the treatment for VZV

Acyclovir

What percentage of common colds are caused by rhinoviruses

30-50%

What are the three species of rhinoviruses

RV-A, RV-B, RV-C (150+ serotypes)

What type of virus are rhinoviruses

Positive-sense, ssRNA non-enveloped viruses

What cell-surface receptors do rhinoviruses bind to

ICAM1, TLR2, CDHR3

What cells do rhinoviruses primarily affect

Airway epithelia (ciliated and non-ciliated)

What percentage of common colds are caused by coronaviruses

10-15%

What percentage of common colds are caused by influenza viruses

5-15%

Are most antiviral drugs effective against the common cold

no

What should future research efforts focus on for the common cold

Non-viral-specific compounds, e.g., broad-spectrum antivirals

Compared to bacterial respiratory pathogens, viral respiratory pathogens are less easily controlled by what

Chemotherapeutics

What do viral respiratory pathogens include

Some of the most prevalent human infections

Are viral respiratory infections mostly acute and self-limiting

yes

How is the diagnosis of viral respiratory infections primarily made

Clinically – symptoms, physical exam, medical history. Further supported by lab techniques

What is the difference between bacterial and viral infections in terms of treatment

Bacterial infections can be treated with antibiotics

viral infections can be treated with antivirals (but antibiotics do not work)

Do viruses reproduce outside living cells

no

What is Streptococcus pyogenes

Group A Streptococcus that can cause strep throat.

More virulent strains are β-haemolytic

Where is S. pyogenes found

In low numbers in the healthy upper respiratory tract – middle ear, throat. Humans are the only reservoir

What are the symptoms of strep throat

Sudden onset pharyngitis, dysphagia, fever

How is S. pyogenes transmitted

via respiratory droplets; saliva/nasal secretions, wound discharge, food (rare).

Facilitated by crowded environments

Are symptomatic or asymptomatic carriers more important for transmission

Symptomatic carriers > asymptomatic carriers

What is scarlet fever

An erythematous rash in children. Can also follow pyoderma/wound infection

What are the signs of strep throat

Beefy red soft palate and uvula

enlarged red tonsils

white or yellow patches on the tonsils

tiny red haemorrhages on the soft palate

What are the signs of scarlet fever

Characteristic red cheeks and rash, white coating on the tongue, strawberry tongue

is Streptococcus pneumoniae group A

no

where does Streptococcus pneumoniae colonise

mucosal surfaces

What diseases does S. pneumoniae cause

Pneumonia, meningitis, otitis media

How does S. pneumoniae establish infection

It translocates to deeper tissues to establish infection in microenvironmental niches

What are the 3 adaptation and survival mechanisms of S. pneumoniae

Sequesters essential metal ions like iron and zinc from host for metabolic needs

scavenging of carbohydrates from host cells to sustain growth and energy production

biofilm formation allows resistance to host immune responses and antibiotics

Why are encapsulated strains of Streptococcus pathogenic

they are harder to kill

How are encapsulated strains identified

Via India Ink stain

What is lysogenic bacteriophage encoding exotoxins

A bacteriophage that integrates its genome into the bacterial chromosome and encodes exotoxins

What is streptococcal toxic shock

A condition caused by S. pyogenes that induces a massive cytokine cascade

What is molecular mimicry

Cell-surface M protein and cross-reactive antigens that resist phagocytosis, aid adherence and epithelial invasion

Are there vaccines against S. pyogenes

no

What is diphtheria

An acute, severe infection affecting nasal and throat mucosa

What causes diphtheria

Corynebacterium diphtheriae

What are the symptoms of diphtheria

Gradual onset, mild fever, sore throat, dysphagia, malaise, loss of appetite

Is diphtheria preventable and treatable

Yes. Largely prevented through vaccination. Previous infection provides resistance

How is diphtheria transmitted

Via airborne droplets

What is the virulence factor of diphtheria

Diphtheria toxin

What does diphtheria toxin cause

Tissue death

What is the hallmark of diphtheria infection

Pseudomembrane

What is the danger of the pseudomembrane

Fatal airway obstruction if dislodged