Lecture 5- Patterns of viral infection

Question 1

Define ‘tropism’

Answer 1

The predisposition of viruses to infect certain tissues and not others

Question 2

What are arboviruses?

Answer 2

Viruses spread by insects

Question 3

Which three factors does tropism depend on?

Answer 3

1) Susceptibility- receptor interactions
2) Permissivity- ability to use host cell to complete replication
3) Accessibility- whether the virus can reach a tissue

Question 4

Which factor affects the tropism of HIV? explain…

Answer 4

Susceptibility:

• HIV usually binds to CD4 and CCR5/CXCR4 receptors
• Delta 32 mutation in CCR5= resistance to HIV
• Some produces lots of chemokine which blocks co-receptor

Question 5

Which receptor do measles have and which host cell receptors do they bind to? * Which receptor does the vaccine strain of measles bind to?

Answer 5

Measles- Haemagglutinin
Host cell: 
- CD155 (SLAM)
- Nectin 4
Vaccine strain of measles uses CD55

Question 6

How does measles infect a person?

Answer 6

• enters through respiratory tract
• Binds to SLAM on dendritic cells
• rides over to the lymph nodes
• binds to more immune cells using SLAM and causes immunosuppression
• Uses NECTIN 4 to leave the host at airway epithelial cells

Question 7

How does influenza enter its host cell?

Answer 7

• Haemagglutinin receptors bind to sialic acid on surface of cells
• enters cell via endosome

Question 8

What causes the influenza virus to change conformation intracellularly? Why does it change conformation?

Answer 8

• low pH in endosome causes conformational change

- Influenza can then fuse with endosomal membrane and uncoats

Question 9

What affects influenza tropism?

Answer 9

• needs particular protease for membrane fusion and uncaring

- only fluid lining the lungs contain the right protease

Question 10

Define pathogenicity

Answer 10

Ability of virus to cause disease

Question 11

Define virulence

Answer 11

Capacity of virus to cause disease

Question 12

What are iatrogenic and nosocomial sources of infection?

Answer 12

1) iatrogenic= as a result of medical treatment (contaminated needles)
2) nosocomial= hospital acquired

Question 13

What is the name of the secondary viraemia caused by VZV? explain how the secondary viraemia is caused

Answer 13

Shingles

• VZV infects skin cells and PBMCs
• VZV infects the sensory neurones and remains latent here
• Shingles (herpes zoster) manifests in adulthood when immunity is impaired. Virus is reactivated in sensory neurone.
• Causes painful rash

Question 14

What are the different patterns of viral infection?

Answer 14

Acute- followed by viral clearance
Persistent- latent, slow, transforming
Long incubations
Oncogenesis- affect cell proliferation

Question 15

What are the different outcomes of an acute infection? Give examples of viruses for each

Answer 15

1) Clearance- with cold and influenza. Adaptive response provides immunity
2) Death- Smallpox (infection of skin) and dengue (leakage of plasma from capillaries)
3) Accidental pathogenesis- polio (paralysis) and rubella in foetus has a tropism for neuronal tissue (Deafness, eye abnormalities and congenital heart disease)

Question 16

What are the two different types of persistent viral infections?

Answer 16

1) Chronic- low level of replication of viruses (papillomavirus in warts)
2) Latent- viral genome remains but symptoms seen at episodes of reactivation when immunity declines (herpes viruses- HSV, VZV)

Question 17

How do viruses remain persistent?

Answer 17

• Evade immune surveillance by MHC down regulation (cytomegalovirus)
• Escape CTLs by mutating (Hep C)
• Infect tissues with reduced immune surveillance e.g. CNS (measles, herpes and papillomavirus-skin)

Question 18

How do viruses cause oncogenesis? Give examples of ontogenetic viruses

Answer 18

• virus may encode oncogenes
• may interfere with cell cycle to enhance their replication
  Examples:
• papillomairus: encodes inhibitors of tumour suppressor p53, E6 and E7 –> forced into S phase
• HHV8 and Merkel cell polyoma
• HTLV-1 causes adult leukaemia

Question 19

What do HBV and HCV cause?

Answer 19

Hepatocellular carcinoma

Question 20

HBV- what sort of virus is it and how is it spread

Answer 20

• Hepadnavirus

- spread by blood and semen

Question 21

What sort of virus is Epstein Barr Virus?

which cancers can it cause

Answer 21

• Gamma herpes virus
• Burkitts lymphoma
• Hodgkins lymph
• Nasopharyngeal carcinoma

Question 22

How is Epstein Barr Virus spread?

Answer 22

In saliva

Question 23

What does the outcome of a virus infection depend on?

Answer 23

• virus sequence
• virus load
• host immune response/ status
• host co-mobidity
• co-infections
• other medications
• host genetics
• host age and gender

Question 24

Give an example of how viral sequence affects a viral infection

Answer 24

Polio

• Sabin, live attenuate vaccine
• Poliomyelitis, invades motor neurone and causes paralysis

Question 25

Give an example of how viral load affects a viral infection

Answer 25

Chickenpox

- older sibling has Midler illness than younger. Second child is in closer contact and is infected by larger viral load

Question 26

Give examples of co-infctions affecting a viral infection

Answer 26

• secondary bacterial infection after influenza
• HHV8 causes Kaposi’s Sarcoma in HIV patients
• Hepatitis Delta virus infects Hep B patients ( causes liver disease+ cirrhosis)

Question 27

Give examples of how genetic resistance and susceptibility affects viral infections

Answer 27

• CCR5 delta 32 mutation= HIV protection

- KIRs- Hep C

Question 28

Which comorbidities predispose patients to influenza

Answer 28

• Asthma
• obesity
• immunosuppression
• immunodeficiency
• elderly
• diabetes mellitus
• pregnancy