Pathogenesis of Acute and Persistent Infections Flashcards
What is the pattern of an acute infection?
A single peak and a swift resolve
What is the pattern of a latent infection?
Multiple peaks with multiple resolves - bursts of acute infection
What is the pattern of an asymptomatic persistent infection?
Virus is produced all the time with no symptoms - virus production remains high with no resolve
What is the pattern of a pathogenic persistent infection?
Peaks of high viral production with resolution but with a constant low level viral production - never fully clears
Describe the features of an acute infection
- Rapid onset of viral reproduction
- Short but potentially severe disease course
- High viraemia
- Immune clearance
What are the benefits to the virus of a persistent infection?
- Continued virus production and transmission of viral genetic material
- With low or no fitness cost to the host, multiple infections generate genetic variability and complexity
- Host’s health not significantly affected (short term), allowing the virus to disseminate to more hosts (same or new environment)
What are the benefits to the host of a persistent infection?
- Persistently infected organisms are resistant to super infections with related viruses (viral accommodation)
- Persistently infected populations can carry and transmit viruses to sensitive populations and eventually settle and/or replace them
- Organisms persistently infected with mutualistic viruses show an increased antiviral response
- Mutualistic viruses can help the host by supplying new genes or through epigenetic changes - can become part of our genome
Describe the typical acute infection course
- Viral entry
- Viral sensing and innate defenses
- Infection establishes
- Adaptive response is induced
- Memory created
- Virus clearance
What is the incubation period?
- Before the symptoms are obvious - measurable and visible
- At the very start of the infection
- Corresponds to time until prodromal symptoms - symptoms before those characteristic of the disease
Is transmission possible in the incubation period?
Yes
What does a short incubation period suggest?
Replication at primary site produces symptoms
What does a long incubation period suggest?
Symptoms occur beyond primary site of infection
What are unapparent acute infections?
- Successful infections
- No symptoms or disease
- Sufficient viral particles produced to spread in the population
- We know we’ve had them due to antibodies
What are the types of Influenza virus?
A, B and C types
Which Influenza type is responsible for pandemics?
A
Which Influenza types cause serious illness?
A and B
Describe antigenic variation
- Shift and drift
- Allows for constant emergence of new strains
Describe Influenza transmission
- Droplets produced during coughing, sneezing and talking
- Contact with contaminated surfaces and then touching our eyes, mouth or nose
- Direct contact with infected individuals
How far can droplet types spread?
- Large infectious droplets = up to 1m
- Small infectious droplets = up to 2m
- Infectious droplet nuclei = over 50m
Describe the pathogenesis of Influenza
- Invades the mucosal surface
- Movement of mucus usually facilitates the downwards movement of the influenza virus
- Spreads in the respiratory tract by replicating in epithelial cells
- Replication in the bronchioles can lead to severe damage in respiratory capacities
- Lower the virus replicates in our respiratory tract the more acute the symptoms become
- Surface receptors determine susceptibility to human vs avian viruses
- Avian = alpha(2,3) sialic acid which is mainly located in the lower respiratory tract and in the cornea
- Human = alpha(2,6) sialic acid which is mainly located in the upper respiratory tract
- Therefore more susceptible to human respiratory viruses
Describe what a human will experience with uncomplicated Influenza
- 1-5 days incubation - depending on the dose and immune status
- Rapid onset of headache, cough and chills
- High fever peaking up to 40 degrees within 24 hours - malaise and myalgia
- Days 2-3 = fever drops - gone by day 6
- In elderly, children or immunocompromised symptoms may worsen or differ
What dictates Influenza pandemic potential?
- Avian viruses re-assorting with human viruses may lead to efficient transmission
- Avian viruses aren’t efficiently transmitted due to lack of avian receptor in the upper respiratory tract
- If an avian influenza virus re-assorts to exchange genetic fragments with a human virus it may create a hybrid avian human virus that will have characteristics of both
- May be able to transmit efficiently from human to human leading to infection with a virus we have very little immunity for so symptoms could be very severe
How are people infected with avian Influenza?
- Direct contact of people working with chickens or birds
- Contaminated surfaces - e.g. bird droppings
- Dissemination of droplets in the air by infected birds - e.g. flapping wings, scratching, shaking their heads
What are the complications of Influenza?
- Primary viral pneumonia
- Secondary bacterial infections
- General muscle pain
- Cardiac pain
- Reye syndrome - rare - brain swelling
How is Influenza treated?
- Antiviral drugs - e.g. tamiflu (oseltamivir), relenza (zanamavir), coumarins (rimantadine)
- Vaccine
- Non-pharmaceutical intervention
What does Norovirus cause?
Gastroenteritis
What is the Norovirus genome?
Small strand RNA virus
What family does Norovirus belong to?
Calciviridae
What is the infectious dose of Norovirus?
Low infectious dose = 1-10 particles
What percentage of enteritis cases does Norovirus make up in the UK?
40%
How is Norovirus transmitted?
Food-borne - faecal-oral transmission
How long do Norovirus symptoms last?
2-3 days
How long are people with Norovirus infectious for?
2 weeks
How many episodes of Norovirus will most people experience in their lifetime?
5
How does Norovirus effect the villi?
- Very stable virus
- Retains infectivity passing through the stomach and GI tract
- Blunts villi in the proximal jejunum - affects exchange process of water in the gut
What does Norovirus do in the gut?
- Needs commensal bacteria for productive infection
- Norovirus binds carbohydrates secreted into the gut lumen by enterocytes or expressed enteric bacteria
- Following transcytosis, Norovirus infects dendritic cells, macrophages and B cells
- Concomitant viral-bacterial antigen presentation during Norovirus infections impacts antiviral immune responses
What products is Norovirus carried by?
- Food/water contamination
- Shellfish
- Berries
- Contaminated either at the source or while being handled
How long is the Norovirus incubation period?
12-48 hours
What symptoms does Norovirus produce?
Rapid and sudden vomiting (children) or diarrhoea (adults) lasting 2 days
Does infection produce long-term immunity to Norovirus?
No - makes vaccine difficult to develop
What is a decision point?
The point where the cell recovers and clears the virus or progresses to a chronic infection
What is clinical latency?
No symptoms but the virus is still replicating
What is virological latency?
No replication in the period where they don’t cause symptoms
What are the general properties of latent infections?
- Low concentration or absence of viral gene products essential for production replication
- Cells latently infected are hidden or poorly recognised by the immune system
- Viral genome persists and can re-initiate productive infection as and when needed to spread infection to new hosts
