Mechanism of viral infection and pathogenesis

Question 1

How many human herpes viruses are there?

Answer 1

8

1. Herpes simplex virus type 1 (HHV-1)
   Can cause cold sores
2. Herpes simplex virus type 2 (HHV-2)
3. Varicella zoster virus (HHV-3)
   Causes chicken pox or shingles
4. Epstein-Barr virus (HHV-4)
   Glandular fever
5. Cytomegalovirus (HHV-5)
6. Human herpesvirus 6 (HHV-6)
7. Human herpesvirus 7 (HHV-7)
8. Human herpesvirus 8 (HHV-8)

Question 2

How does virus infection of a host lead to disease?

Answer 2

→ 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 3

What do we know about the Immunopathology of Hepatitis C Virus (HCV)?

Answer 3

→ 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 4

What do we know about the Immunopathology of Dengue Virus?

Answer 4

→ 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 5

What do we know about Influenza?

Answer 5

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 Influenza

Infection generates powerful, long-live immunity
Easy to vaccinate against if you know what’s coming

Question 6

How do we get immunity against the next seasonal flu strain?

Answer 6

You make neutralising antibodies against your last infection

→ Sometimes these are OK against your next infection, sometimes they are not

→ You make a T cell response against your last infection

→ This should be effective against your next infection

Question 7

What does the outcome of an infection depend on?

Answer 7

→ The outcome of an infection depends on what you are you infected by, whether you’ve seen it (or anything like it) before, and the state of your immune system

so not just the pathogen itself!