Mechanisms of Viral Infection and Pathogenesis Flashcards
Sites of microbe entry
Conjunctiva Respiratory Tract Alimentary Tract Urogenital Tract Scratch, injury Skin Anus Arthropod → Capillary
General Pattern of an Acute Viral Infection
Disease symptoms present when the virus is at its highest titre (highest viral load).
This will make you ill, and the immune system responds to the virus by getting rid of it, allowing you to recover.
Generally, you develop long-lasting protective immunity (principle behind vaccines as well).
Examples of acute viral infections
Common cold Measles Ebola Smallpox Influenza
Common cold virus presentation
The common cold is an upper respiratory tract infection and the immune system resolves this.
Measles presentation
Typical spots and ulcerations of the tongue
- patients find it difficult to eat
- serious CNS problems
Ebola presentation
Complete destruction of the endothelia, massive haemorrhaging causing internal bleeding (these people usually bleed to death).
Therefore, the immune system does not always resolve this acute infection
Types of chronic viral infection
Latent, Reactivating Infection
Persistent Infection
General Pattern of Chronic Viral Infection: Latent, Reactivating Infection
At the beginning of infection, there is a burst of viral replication and disease (like acute infection), the immune system brings this under control so you are disease free.
But, throughout life, there are episodic reactivations of the virus, meaning there is a virus reservoir in the host which is controlled by immunity. If the immune system breaks down in any way, you can get reactivation of the virus, with disease symptoms presenting again.
Example of a reactivating latent viral infection
Herpes virus
-dsDNA genome
How many herpes viruses are there?
8
Different herpes viruses and their effects
Once you get infected with herpes viruses you can’t get rid of them, meaning it is a life-long infection, but they are controlled by immunity.
HHV-1 → classic herpes virus
HHV-2 → genital herpes
HHV-3 (VZV) → chicken pox
HHV-4 (EBV)→ mononucleosis (glandular fever)
HHV-5 (CMV)→ mononucleosis (glandular fever)
HHV-8 (KSHV) → Kaposi’s sarcoma
HHV-1 Presentation
Primary Gingivostomatitis is the initial infection with HHV-1, characterised by a spotty rash in kids. Immune system then acts upon this.
Virus Reactivation during immune stress
- cold sores (local)
- no primary rash
HHV-3 Presentation
HHV-3 (VZV) causes a disseminated rash.
If you get this early enough in life it is effectively harmless, but the later you get it the worse it is.
Virus Reactivation during immune stress
-shingles (local)
What do all herpes virus have in common in relation to their effects on the body?
All of the herpes viruses give you specific fevers during their primary infections
Which herpes viruses develop latency in neurones? Which neurones specifically?
Herpes Simplex & VZV
-sensory neurones in dorsal root ganglion
How do Herpes simplex and VZV develop latency?
In both herpes simplex and VZV, the viruses travel up neurones and establish persistent infection in sensory neurones in dorsal root ganglion where the virus is largely switched off and immune system keeps it so.
Later on, a secondary stimulus (e.g. immunosuppression) can cause the virus to activate in the neurone and for the virus to travel back down the peripheral nerve, causing local infections (cold sore/shingles) in much more specifically localised regions where the tissue is innervated by infected neurone.
General Pattern of a Chronic Viral Infection: Persistent Infection
Persistent infections have two separate patterns.
First pattern:
- virus peaks with an initial infection, and then immune system gets rid of it.
- no symptoms present for a very long time and then you get an eruption of the virus, causing disease (e.g. HIV)
Second pattern:
- rubella infection when pregnant
- if this happens early enough in the first trimester, your immune system will not recognise that as foreign and sees it as ‘self’, and so the unborn foetus is immunotolerant of this virus
- virus will tear through the tissues, causing congenital rubella
- hence why vaccinations are so important!
Examples of Persistent Viral Infections
HIV
· Virus infects CD4+ T cells and weakens immune system
HCV (Hepatitis Virus C)
· Virus infects hepatocytes and damages liver
Congenital Rubella
· If infected in utero, virus is seen as self, baby is born immunotolerant and virus continues to replicate (and cause damage) in neonatal tissues
How does virus infection of a host lead to disease?
Pathogenesis results from cell and tissue cytopathic damage caused by the viral infection. On most occasions, the damage is limited by the host’s immune system.
What is considered a ‘successful’ virus?
A successful virus is one that replicates well enough to spread to the next host
-does not have to cause disease (many infections are apathogenic)
Cytopathic damage of Ebola
EBOLA targets vascular endothelial cells, causing lots of haemorrhagic lesions
Cytopathic damage of Influenza A
Respiratory epithelial cells are lined with cilia which beat to expel mucus to get rid of any foreign substances.
The influenza infection (red stain in the pic) targets lung epithelia and destroy the cilia, so you can’t clear the virus.
Cytopathic damage of RSV
The RSV infects respiratory epithelia and all the cells fuse together
-loads of nuclei all inside one cell→non-functional cell
What is a way in which a virus causes disease without viral damage (non-cytopathic)?
Virus can induce immunopathology
-disease caused by dysfunction of immune system
Examples of viruses which can induce immunopathology
Hepatitis C Virus (HCV)
Dengue Virus
Hepatitis C Virus (HCV): Course of illness
HCV causes classical acute infection which is permanently cured by the immune system in ~20% cases.
Acute infection progresses to chronic liver inflammation ~80% cases. This continues to fibrosis and eventually you get severe liver damage (cirrhosis/hepatic cancer).
Which cells does HCV infect?
hepatocytes
How does HCV cause immunopathology and lead to liver disease?
Actual virus doesn’t cause damage to the hepatocytes it has infected (non-cytopathic), but immune system does:
- virus broken down by immune system into peptides
- peptides presented on surface of hepatocytes through MHC Class I
- immune system recognises this as foreign and attacks it
- pro-inflammatory cytokines, leukocytes etc. attempt to clear infected cells
- CD8+ T cells destroy infected cells
- liver therefore fails
Dengue Fever
Mosquito-borne virus infection which is characterised by mild symptoms (flu-like symptoms and hospitalisation not needed):
- mild fever
- skin rash
- headache
- bone and muscle pain
- nausea
- vomiting
How many serotypes of Dengue virus are there?
There are 4 serotypes (1-4), all of which have the same clinical manifestations
How does Dengue Virus induce immunopathology?
SECOND INFECTION by a different serotype from the first infection (secondary heterotypic infection). You develop more serious disease symptoms:
- Acute fever
- Severe abdominal pain
- Headache
- Plasma leakage
- Intravascular volume depletion
- Coagulation dysfunction
Severe dengue may include dengue shock syndrome (DSS) and haemorrhage
· Antibodies formed in response to dengue infection are not cross-protective against other subtypes of the virus. In fact, they may result in more severe disease due to a phenomenon known as antibody-dependent enhancement (ADE)
· Non-neutralising antibodies coat virus, forming immune complexes which get internalised into macrophages through their Fc receptors; fixation of complement by circulating immune complexes results in release of products of the complement cascade leading to sudden increased vascular permeability → shock and death
Pathology of Influenza
· Mild upper respiratory tract infection to severe lower respiratory tract infection
· Lower respiratory tract infection causing damage to lung epithelial and viral pneumonia, often secondary pneumonia
· Fever, often prolonged
· Neurological (headache, malaise)
· Myalgia
What does Influenza infection generate in the long-term?
long-lived immunity
Antigenic Shift
changes in surface antigens that occur when viruses exchange genetic material with other strains
