Lecture 21: Consequences of Viral Infection

Question 1

What is pathogenesis?

Answer 1

The ability/capacity of the virus to cause disease

Question 2

What does the virulence quantify?

Answer 2

How pathogenic a virus is

Question 3

How can virulence be quantified?

Answer 3

Virus titre

Mean time to death: e.g: mice infected then time required to cause death in 50% of animals is calculated

Mean time to appearance of disease

Measurement of fever, weight loss

Measurement of pathological lesions (poliovirus)

Reduction in CD4 T cell (HIV)

Case fatality ratio/ hospitalization rate…

Question 4

How do we study viral pathogenesis?

Answer 4

• We inject the host and observe the symptoms they produce
• We can inject the host with animal viruses that can be used as models for human disease

OR

• We can genetically modify animals to produce human viruses e.g. by modifying their immune system by adding or deleting cells that prevent a disease from being expressed, or introducing viral genes that code for receptors that bind to viruses.

Question 5

Is it true that mice don’t have the CD155 receptor that poliovirus binds to, so they can be injected with the gene that codes for this receptor?

Answer 5

Yes

Question 6

After having the CD155 receptor, what happened when the mice were injected with poliovirus?

Answer 6

They showed signs of paralysis, a symptom of poliovirus

Question 7

How many types of poliovirus are there that all have different virulence to one another?

Answer 7

There are 3 types of poliovirus and they all have different virulence to one another. Type 2 is more virulent than type 1.

Question 8

What are the mechanisms of viral injury and disease?

Answer 8

• Direct viral Cytotoxicity/Killing (non-enveloped viruses)
• Virus-induced immune Pathogenesis
• Virus-induced immune Suppression
• Virus induced transformation

Question 9

Describe direct virus killing

Answer 9

• Causes damage to the host cell as a result of viral replication within the host cell i.e Poliovirus, which kills neurons and causes muscle paralysis

Question 10

Describe Virus-induced immune Pathogenesis

Answer 10

• Tissue damage due to the host’s immune system recognising the virus replicating within the host and hence immune system can carry out defence mechanisms, such as: apoptosis, or immune responses that target virus-infected cells.

Question 11

What are some examples of viruses that cause Virus-induced Immunopathogenesis?

Answer 11

• HBV (hepatitis B virus)
• HBV infects hepatocytes. Viral antigens are presented on the outer membrane of these hepatocytes and recognised by cytotoxic T cells.
• HCV (hepatitis C virus)
• Antibody-antigen complexes form and deposit within small blood vessels, leading to the development of inflammation (vasculitis) when the immune system tried to destroy these complexes.
• Cytokines produced as a result of ebola infection and detection by immune system results in the damage of vascular endothelial cells, causing haemorrhage.

Question 12

Describe Virus-induced immune Suppression

Answer 12

• Some viruses can specifically target and infect cells of the immune system causing immunodeficiency.
• The most prominent of these is HIV infection, which is known to cause AIDS

Question 13

Describe Virus Induced Transformation

Answer 13

• This is caused when certain viruses cause immune suppression and hence, the promotion of tumour development
• For example, a person can be infected with HPV. HPV encodes E6 and E7, which are proteins that can encode for cancer cells.
• There are multiple HPV genotypes, and the risk of developing HPV associated cervical cancer is much greater with certain high risk HPVs (HPV16 , HPV18)

Question 14

What type of genome does HPV16 have?

Answer 14

A small, circular genome, that contains genes E6 and E7. These encode for cnacer cells. However, they can be bound to by tumour supressors in the host, which will degrade these genes

Question 15

Viral virulence Genes

Answer 15

Gene products that affect viral replication

Genes encoding toxins

Genes encoding modulators of the immune response

Oncogenes

Gene products that enable the virus to spread in the host

Question 16

Viral toxic proteins

Answer 16

• NSP4 is a nonstructural glycoprotein of rotavirus (it’s a viral endotoxin).
• NSP4 inhibits the sodium-glucose transporter, resulting in leaks, and these leaks manifest as diarrhoea.
• The presence of the CCR5 receptor on host immune cells reduces the susceptability to HIV. People with the mutation encoding for CCR5 won’t get HIV

Question 17

Do virulent genes always encode for proteins?

Answer 17

No, virulent genes aren’t always encoding (check: i.e, Poliovirus doesn’t have a 5’ cap on its +ve sense mRNA, so translation can’t be initiated)

Question 18

Why can young age sometimes be a determiner of virulence?

Answer 18

If a person is very young, they may have an immature immune response

Question 19

Why can old age sometimes be a determine of virulence?

Answer 19

Because:

• Less elastic alveoli
• Weaker respiratory muscles
• Diminished cough reflex
• Reduced rate of production of new immune cells