6.2.3 Pathogenesis

Question 1

What are the stages of viral infection?

Answer 1

routes of entry

viral spread/dissemination in the host

virus replication

shedding

Question 2

What determines the host range of a virus?

Answer 2

Tropism (it’s all about receptors)

Question 3

What are the possible entry portals for viruses? (6)

Answer 3

skin

GIT

respiratory system

blood (insect bites, injections etc)

genital

transplacental

Question 4

What are the innate defences of the skin?

Answer 4

keratinised - effective barrier

must be breached by abrasions or bites

macrophages, neutrophils, dendritic cells, natural killer cells

Question 5

What are the defences of respiratory tract?

Answer 5

Mucociliary escalator (in URT and bronchii)

Resident commensal bacteria in URT

sneezing and coughing

innate immunological defences

Question 6

How can viruses enter the resp tract?

Answer 6

aerosolized droplets expelled by an infected individual

spread by coughing or sneezing

contact with saliva from an infected individual

Question 7

What are the defences of GIT? (5)

Answer 7

low pH in stomach denatures protein and kills most microorganisms

bile and proteolytic enzymes in intestines

high pH in duodenum (rapid change)

commensal bacteria (out complete pathogenic bacteria)

mucous and secretory IgA in the intestinal tract

Question 8

How can viruses enter via blood?

Answer 8

via haematophagous (blood biting) insects

via blood products and/or sexual contact

Question 9

How can viruses enter via genital tract?

Answer 9

via infected semen

Question 10

How can viruses enter transplacentally?

Answer 10

viraemic pregnant animals can transmit virus to foetus in utero

Question 11

What are two types of infections?

Answer 11

local

spreading (via blood, lymphatics, CNS, immune cells)

Question 12

Describe local infections

Answer 12

replication in epithelium at initial infection site

cell-to-cell spread, but don’t disseminate to other tissues

usually acute (short incubation period, short duration)

site of shedding = site of entry

Question 13

Describe systemic infections

Answer 13

primary replication at entry site followed by spread to other distant sites

allows entry and exit routes from host to differ

usually longer incubation period and more severe pathology

greater involvement of adaptive immune responses

Question 14

What is viraemia?

Answer 14

haematogenous spread

Question 15

What is primary viraemia?

Answer 15

spread of virus by blood from entry site to other target tissues, e.g. liver, spleen

Question 16

What is secondary viraemia?

Answer 16

may occur following replication in secondary sites

usually allow higher viral titres and further dissemination to other sites

Question 17

How does rabies spread?

Answer 17

introduction via bite

primary replication in muscle cells

uses motor neurons to reach CNS

further replication in spinal cord and brain

enters salivary glands for onwards transmission

Question 18

Where does the virus reach the highest titre?

Answer 18

in organ tissues from which it is shed

Question 19

How do viruses induce pathology?

Answer 19

Direct effects:
-CPE
-cell stimulation
-cell transformation (tumour formation)

Indirect effects
-immune mediated pathology

Question 20

What causes CPE?

Answer 20

inhibition of host protein and RNA synthesis (cell can’t repair itself)

lysosomal damage (leakage of enzyme)

cell membrane abnormalities

cell lysis (non-enveloped viruses)

apoptosis

Question 21

what is a negri body?

Answer 21

Round or oval inclusion bodies that contain ribonuclear viral proteins
only in rabies

Question 22

What are syncytia?

Answer 22

large, multinuclear ‘giant cells’ caused by virus infected cells

Question 23

Describe the mechanism of cell stimulation

Answer 23

Poxvirus-infected cells synthesise epidermal growth factor-like protein

stimulates cell cycle of neighbouring cells

makes them ideal infection targets for viral replication (virus can spread to newly dividing cells)

Question 24

What determines disease?

Answer 24

host, viral and environmental factors

Question 25

What host factors influence disease outcome?

Answer 25

-age
-gender
-nutritional status
-species/breed
-immune status of host
-physiological stress
-co-infections of multiple pathogens

Question 26

What viral properties impact disease?

Answer 26

-geographical origin
-transmission route
-infectivity
-immunosuppression

Question 27

What are viral virulence factors?

Answer 27

molecules produced by viruses that enable them to invade the host, replicate and disseminate by subverting or eluding host defences

Question 28

What environmental factors can influence disease outcome?

Answer 28

• environment contamination
  -climate conditions
  -quality of nutrition
  -stocking density
  -management practices
  -veterinary policy

Question 29

Describe acute infection

Answer 29

virus causes a rapid, self limiting infection

infection cleared by the immune system leading to recovery

Question 30

How can we divide persistent infections?

Answer 30

latent

chronic

Question 31

Describe latent infections

Answer 31

Virus persists at very low levels following recovery (Quiescent/latent state)

Potential to reactivate (switch from latent to productive infection

Question 32

What is a chronic infection?

Answer 32

persistent infection at low levels, following recovery will persist at low lvls

almost eliminated, but then hide in immune-privileged sites (e.g. CNS) and then attack again

don’t cause acute infection, grow slowly in a host until they reach sufficient lvls to cause disease

Question 33

What factors are involved in persistence?

Answer 33

• immune evasion
• tolerance
• virus varients with with antigenic variation
  -replication in privilidged sites (to avoid being detected)
  -immune suppression