Mechanism of Viral Infection and Pathogenesis

Question 1

What are the general stages of viral infection?

Answer 1

The first is acute infection:
- Something infects us and has a limiting life span
- The disease symptoms respond to the peak of viral load
Chronic infections of which there are two types
Latent, reactivating infection:
- You get viremia symptoms, it gets resolved
- Sometimes you get another wave of viremia with or without symptoms
- Life long infection, controlled by immunity
Persistent infection:
- An initial round of viremia followed by a very low viral load followed by an end of life eruption in virus again- e.g. HIV
- Or you get an early wave of viremia but the viral load stays up, your immune system does not bring it under control e.g. congenital rubella

Question 2

How do Herpes Simplex and VZV reach latency?

Answer 2

The viruses migrate into sensory neurons of the dorsal root ganglion into an immunoprivilage site
They establish a latent infection, switch off most of their protein production
At some point you get an insult to your immune system such as sunlight or a cold, your immune system is depressed so the virus moves out of its latent state
Goes back into specific tissues and causes a local eruption of the virus

Question 3

How is congenital rubella a persistent infection?

Answer 3

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
Congenital Rubella:
- Rubella virus viremia can infect the placenta of pregnant women, and viral replication can infect all foetal organs. Causes huge amount of tissue damage
- The hallmark of foetal infection is chronic infection that persists throughout foetal life, with shedding of virus up to 2 years after birth
- Viral shedding by infants with congenital rubella syndrome can result in outbreaks

Question 4

How does virus infection of a host lead to disease?

Answer 4

Many infections are apathogenic or associated with relatively mild symptoms; it is important to realize that from the virus’ point of view these are not always failed or resolved infections – a successful virus is one that replicates well enough to spread to the next host
Pathogenesis results from cell and tissue damage caused by the viral infection. On most occasions the damage is limited by the host’s immune system
On some occasions the relative limited damage caused by the virus is made worse or even caused by the host’s immune system (= immunopathology)

Question 5

What is viral hepatitis?

Answer 5

Caused by hepatitis C
You get an acute infection
Normally most are cured
Some develop chronic disease characterised by chronic inflammation leading to liver fibrosis and then either cirrhosis and/or sometimes liver cancer

Question 6

What is the immunopathology of Hepatitis C Virus like?

Answer 6

Chronic hepatitis is a disease of severe liver damage and loss of hepatocytes – caused by persistent HCV infection
HCV is non-cytopathic
Hepatitis associated with extensive liver infiltration of leukocytes
Pro-inflammatory cytokine levels very high
Viral clearance and disease is associated with generation and infiltration of CD8+ cells which attack infected cells and destroy them
HCV persistence is associated with the generation of HCV variants that are not recognised by CD8+ cells

Question 7

What is the immunopathology of dengue fever like?

Answer 7

Severe dengue, which may include dengue shock syndrome (DSS), and hemorrhage

- Greatest risk is a previous infection with a different serotype
- Antibodies formed in response to a 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 or ADE
- Non-neutralizing antibodies coat virus, forming immune complexes which get internalised into mononuclear phagocytes 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

Question 8

What effect does RSV have on immunopathology?

Answer 8

RSV infections in early life show unbalanced Th1/Th2 responses

- This depresses inflammatory cytokine production, CD8+ responses and IgG production, meaning clearance is slow and development of memory is poor
- This enhances IgE production, leading to allergy/asthma on re-exposure

Question 9

What effect does influenza have?

Answer 9

People of all ages are infected, usually only a serious problem in the old or children with asthma
Pathology
- Mild URTI to severe LRTI
- Lower respiratory tract infection causing damage to lung epithelia and viral pneumonia, often secondary pneumonia
- Fever, often prolonged
- Neurological (headache, malaise)
- Myalgia- sore muscles
Infection generates powerful, long-live immunity
Easy to vaccinate against if you know what’s coming