Mechanism of viral infection and pathogenesis

Question 1

What are sites of microbe entry?

Answer 1

○ Conjunctiva 
○ Respiratory tract
○ Scratch/injury
○ Alimentary tract
○ Urogenital tract 
○ Skin
○ Anus 
○ Capillary

Question 2

What are the general patterns of viral infection?

Answer 2

1. Acute infections
2. Chronic infections
3. Latent/reactivating infections

Question 3

What do you generally develop after acute infections?

Answer 3

○ Generally develop long-lasting immunity against these diseases

Question 4

What happens to virus in chronic infections?

Answer 4

○ Virus persists throughout life and so must be kept under control

Question 5

What is there a burst of in chronic infections and what happens throughout life?

Answer 5

○ Burst of viral replication
▪ Immune system brings this under control so you are disease free
▪ Throughout your life there are episodic reactivations of the virus as the virus has not been destroyed
§ Can get disease symptoms returning

Question 6

What is an example of a latent/reactivating infections?

Answer 6

○ Human Herpes Viruses

§ Life-long infection

Question 7

What is the human herpes virus controlled by?

Answer 7

Controlled by immunity

Question 8

What are the symptoms of herpes simplex virus(HHV-1)?

Answer 8

▪ Primary gingivostomatitis

Question 9

What do the symptoms of herpes simplex virus(HHV-1) come back as in times of stress when the virus is reactivated?

Answer 9

▪ Comes back later as a cold sore in times of stress when virus is reactivated

Question 10

What does the chickenpox(HHV-3) virus symptoms come back as when the virus is reactivated?

Answer 10

▪ Comes back as the shingles when virus is reactivated

Question 11

Why is HIV a persistent infection?

Answer 11

▪ HIV: virus infects CD4+ cells and weakens immune system

Question 12

Why is HCV a persistent infection?

Answer 12

▪ HCV: virus infects hepatocytes and damages liver

Question 13

What happens if congenital rubella is infected in utero and what damage does this cause?

Answer 13

If infected in utero, virus is seen as self, baby is born immunotolerant and virus continues to replicate and cause damage in neonatal tissues

Question 14

What does herpes give during a primary infection?

Answer 14

○ During a primary infection, herpes gives you very specific fevers

Question 15

What does the herpes simplex virus give in children?

Answer 15

○ Disseminated rash (herpes simplex virus) in the child

Question 16

What virus causes chickenpox and what is it?

Answer 16

○ Chickenpox (varicella virus) are a delocalised rash all over the body

Question 17

In both the herpes simplex virus and varicella virus, where do the viruses travel and what does a secondary stimulus cause?

Answer 17

○ In both these cases, both the viruses travel up neurons and establish a persistent infection where the virus is switched off
§ Secondary stimulus causes them to travel back down the neuron and cause infection locally i.e. cold sore/rash

Question 18

What defines a successful virus?

Answer 18

○ A successful virus is one that replicates well enough to spread to the next host

Question 19

What does pathogenesis result from?

Answer 19

○ Pathogenesis results from cell and tissue damage caused by the viral infection

Question 20

What does tissue damage cause the release of?

Answer 20

○ Tissue damage causes release of viral debris and the immune system is primed

Question 21

Example of an inapparent infection

Answer 21

○ 90% of all polio virus infections in unvaccinated individuals are asymptomatic (inapparent)

Question 22

What do many people get infected without celar symptoms of and what is a symptom that is presented?

Answer 22

○ Many of us get infected with parainfluenzavirus 5 without clear symptoms
§ Presents with normal cough

Question 23

What diseases are known to cause cytopathic damage?

Answer 23

Ebola

Question 24

What does ebola target and what receptors does it bind to?

Answer 24

○ Ebola targets vascular endothelial cells

§ Binds to receptors that are only expressed on vascular endothelia

Question 25

What does the influenza virus target?

Answer 25

○ Influenza virus targets lung epithelia

Question 26

What does RSV induce in lung epithelia?

Answer 26

○ RSV induces syncytia in lung epithelia

Question 27

What is chronic hepatitis a disease of and caused by what infection?

Answer 27

○ Chronic hepatitis is a disease of severe liver damage and loss of hepatocytes – caused by persistent HCV infection

Question 28

Can you be vaccinated for chronic hepatitis?

Answer 28

Cannot be vaccinated against this disease

Question 29

Why does HCV cause disease, despite it being non-cytopathic and hence why does the patient die?

Answer 29

○ If non-cytopathic, it should not cause disease but it does because: ▪ Although the virus causes no damage to the cell its infected, it is broken down by normal function of immune system ▪ Peptides from the virus get presented on surface of hepatocytes through MHC class I ▪ Signals to the immune system that there is a foreign body so immune system attacks ▪ Liver gets full with inflammatory response cells (pro-inflammatory cytokines, leukocytes) which will attempt to clear the infected cells ▪ T cells (CD8 cytotoxic cells) will destroy infected cells § So you die because you destroy your own liver

Question 30

What does HCV start by causing?

Answer 30

HCV starts by causing a classical acute infection

Question 31

What is hepatitis associated with?

Answer 31

○ Hepatitis associated with extensive liver infiltration of leukocytes

Question 32

What happens to the levels of pro-inflammatory cytokine in hepatitis?

Answer 32

○ Pro-inflammatory cytokine levels very high

Question 33

What is viral clearance and disease associated with?

Answer 33

○ Viral clearance and disease is associated with generation and infiltration of CD8+ cells which attack infected cells and destroy them

Question 34

What is HCV persistence associated with?

Answer 34

HCV persistence is associated with the generation of HCV variants that are not recognised by CD8+ cells

Question 35

What is the most common mosquito-borne infection?

Answer 35

Dengue Fever

Question 36

What are the symptoms of a primary infection of dengue fever?

Answer 36

``` ○ Mild fever ○ Skin rash ○ Headache ○ Bone and muscle pain ○ Nausea ○ Vomiting ```

Question 37

What are the symptoms of secondary heterotypic infection of dengue fever?

Answer 37

``` ○ Acute fever ○ Severe abdominal pain ○ Headache ○ Plasma leakage ○ Intravascular volume ○ Depletion ○ Coagulation and dysfunction – can bleed out ```

Question 38

Why can antibodies formed in response to a dengue infection result in more severe disease and what is this known as?

Answer 38

○ Antibodies formed in response to a dengue infection are not cross-protective against other subtypes of the virus (i.e. protection against dengue virus 1 will not protect you against any other strains) § In fact they may result in more severe disease due to a phenomenon known as antibody-dependent enhancement or ADE

Question 39

What do non-neutralizing antibodies do and what does this result in?

Answer 39

○ Non-neutralizing antibodies coat virus, forming immune complexes ▪ These get internalised into mononuclear phagocytes through their Fc receptors; fixation of complement by circulating immune complexes ▪ This results in release of products of the complement cascade leading to sudden increased vascular permeability, shock and death

Question 40

What is the pathology of influenza?

Answer 40

○ Mild URTI (upper respiratory tract infection) 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