Lecture 12 - Pathogenesis of Viral Infections I

Question 1

Proportion of the population infected with a herpesvirus

Answer 1

98%

Question 2

Why does most contact with viruses not result in symptoms?
1)
2)
3)

Answer 2

1) Particles don’t find a cell to infect
2) Particles are destroyed or inactivated as they enter the host
3) Infections don’t progress beyond one or two host cells

Question 3

How can viral sensitivity to heat, drying or sunlight (UV) be overcome?

Answer 3

Produce a large number of viral particles

Question 4

How can viruses avoid contact with the outside environment?

Answer 4

Insect vectors (arboviruses)
Transfer via body fluids.  Not outside host for long

Question 5

What must a virus do to cause infection?
1)
2)
3)

Answer 5

1) Gain entry to body
2) Multiply and spread
3) Target appropriate organ

Question 6

How can a virus be maintained in nature?
1)
2)
3)

Answer 6

1) Shed into the environment
2) Taken up by an arthropod vector or needle
3) Passed congenially (mother to foetus transmission)

Question 7

Example of a systemic infection

Answer 7

Polio.

Enters via faecal/oral route, spreads to CNS

Question 8

Example of a local infection

Answer 8

Influenza.

Enters, replicates, is transmitted from respiratory tract

Question 9

What determines the length of infection?

Answer 9

Immune response of the host

Question 10

Tropism of a virus

Answer 10

Anatomical localisation of a virus

Question 11

Does the human body present many ways for a virus to enter?

Answer 11

No. A limited spectrum of entry sites is provided

Question 12

Viruses transmitted to the skin via mechanical trauma
1)
2)
3)
4)
5)

Answer 12

1) HPV
2) HIV
3) HSV
4) HBV
5) Poxvirus

Question 13

Viruses transmitted by injection

Answer 13

HBV, HIV

Question 14

Virus transmitted by bite of an infected animal

Answer 14

Rabiesvirus

Question 15

General behaviour of viruses that infect via the skin

Answer 15

Don’t multiply locally, but migrate to other tissues.

EG: HBV, arboviruses enter bloodstream. Rabiesvirus migrates along nerves

Question 16

Most important site of viral entry

Answer 16

Respiratory tract

Question 17

How do viruses enter the respiratory tract

Answer 17

Via aerosol inhalation or mechanical transmission of infected nasal secretions

Question 18

Sites of virus deposition by droplet size
1)
2)
3)

Answer 18

1) Over 10 micrometers - Lodge in nose
2) Between 5-10 micrometers - Lodge in airways
3) Under 5 micrometers - Enter alveoli

Question 19

Barriers to infection of the respiratory tract
1)
2)
3)
4)
5)

Answer 19

1) Mucus
2) Cilia
3) Alveolar macrophages
4) Temperature gradient
5) IgA

Question 20

How do viruses infect the respiratory tract?

Answer 20

Bind to receptors on epithelial cells

Question 21

Amount of mucus produced per day by a healthy person

Answer 21

20-200mL per day in nose and lungs

Question 22

How fast does the muco-ciliary elevator move liquid from lungs to oesophagus?

Answer 22

~1cm/minute

Question 23

Viruses that can infect the LRT
1)
2)
3)
4)

Answer 23

1) Parainfluenza virus
2) Respiratory syncitial virus
3) Influenza virus
4) Adenovirus

Question 24

Viruses that can infect the URT
1)
2)
3)
4)
5)
6)
7)

Answer 24

1) Rhinovirus
2) Parainfluenzavirus
3) Respiratory syncitial virus
4) Influenza virus
5) Adenovirus
6) Herpes simplex virus
7) EBV

Question 25

Hepatitis that can be sexually transmitted

Answer 25

HBV

Question 26

Viruses that cause local GIT infection

Answer 26

Rotavirus, coronavirus, adenovirus

Question 27

Viruses that enter via the GIT to cause systemic infection

Answer 27

Enteroviruses, hepatits A

Question 28

Virus survival requirements if infecting the GIT

Answer 28

Acid stability Resistance to bile salts (basic) Resistance to inactivation by proteolytic enzymes (in the case of reoviruses, proteolytic cleavage is necessary)

Question 29

Cell often used by viruses to infect the small intestine

Answer 29

M cells

Question 30

Only enveloped viruses that can infect the GIT

Answer 30

Coronaviruses. | Can be protected from acid by association with milk products

Question 31

How can a virus infect GIT if it lacks receptors for epithelial cells?

Answer 31

HIV, Hep B can infect anal route via abrasions in epithelium

Question 32

Viral spread beyond site of infection

Answer 32

Disseminated

Question 33

Viral spread beyond site of infection, affecting multiple organs

Answer 33

Systemic

Question 34

Examples of local respiratory viruses

Answer 34

Influenza, rhinoviruses, respiratory syncitia virus

Question 35

Example of local dermatological virus

Answer 35

HPV

Question 36

Example of local GIT virus

Answer 36

Rotavirus

Question 37

How can viruses target whether to become local or systemic?

Answer 37

Target viral budding to apical or basal surface of host cell. This might occur via viral glycoproteins.

Question 38

Viremia

Answer 38

Presence of viral particles in the blood

Question 39

Types of viremia

Answer 39

Passive viremia - Viral particles introduced to blood without viral replication at the site of entry (EG: injection, animal bite) Active viremia - Presence of newly-synthesised virions in blood

Question 40

Where can viruses be during viremia?

Answer 40

Free in blood, or within infected cells in blood

Question 41

Primary and secondary viremia

Answer 41

Primary - Released from infected cells at the site of entry. Lower viral titres. Secondary - Virus has infected a different target organ to the site of entry (often the spleen or liver). Larger viral titres, more prolonged viremia.

Question 42

How is viremia in plasma neutralised?

Answer 42

Neutralised by antibodies, removed by macrophages

Question 43

How long does it take for the body to control viremia free in the plasma?

Answer 43

1-2 weeks for a neutralising antibody response

Question 44

Examples of viruses causing cell-associated viremia

Answer 44

Measles HIV Measles and HIV spread in monocytes. HIV spread in CD4+ T cells

Question 45

Days after infection that primary viremia can occur

Answer 45

~2 days

Question 46

Days after infection that secondary viremia can occur

Answer 46

~4-14 days

Question 47

Stages of viremia in mousepox

Answer 47

Primary viremia after two days, replication occurs in skin, regional lymph nodes Secondary viremia after five days. Replication in spleen and liver.

Question 48

Haematogenous spread

Answer 48

Epithelium at body surface drains into lymphatic capillary. This drains to lymph node, which drains to venous system

Question 49

``` Different strategies of tissue invasion from the blood 1) 2) 3) 4) ```

Answer 49

1) Some viruses can infect endothelial cells in blood vessels, infect tissues from the blood 2) Transport across endothelial cells via transcytosis 3) Virus can infect monocytes or lymphocytes, which can cross from blood into tissues 4) Some tissues aren't joined via tight junctions. EG: mumps moves between cells of chorioid plexus from blood into the brain

Question 50

``` How do viruses spread neurally? 1) 2) 3) 4) 5) ```

Answer 50

1) Via peripheral nerves (EG: HSV, varicella, rabies) 2) Uncoated nucleocapsid is carried passively along axons or dendrites 3) Virus multiplies in nerve body. Progeny can cross synaptic junction, infect CNS 4) Protected from CD8+ attack, as neurons lack MHCI 5) Some viruses enter directly from blood

Question 51

``` Rabiesvirus neural spread 1) 2) 3) 4) 5) ```

Answer 51

1) Replicates at site of infection (often myocytes) until enough viral particles come into contact with sensory or motor nerve cells 2) Virus enters axons where they aren't myelinated 3) Move to neuron nucleus via retrograde axoplasmic flow 4) Rabies reaches spinal cord. Clinical rabies occurs when neuronal dysfunction begins. 5) Virus travels along peripheral nerves via anteretrograde axoplasmic flow to salivary glands.

Question 52

How quickly does rabies virus travel along axons?

Answer 52

Slowly. | ~10-20mm/day

Question 53

Virus that travels from a reservoir to epithelium via anteretrograde transport

Answer 53

Herpesvirus

Question 54

Spread of varicella zoster (herpesviridae)

Answer 54

Day 0) Infection of conjunctiva and URT - Viral replication in local lymph nodes Day 4-6) Primary viremia in bloodstream -Further replication in liver and spleen. Secondary viremia/ Day 10) Infection of skin, vesicular rash

Question 55

Virus that uses both viremia and neural spread

Answer 55

Variacella zoster. Viremia from replication in lymph nodes, spleen, liver. Dormancy in dorsal root ganglia

Question 56

Viruses that kill foetuses

Answer 56

Cytocidal viruses

Question 57

Viruses that result in abnormalities of foetuses

Answer 57

Non-cytocidal viruses

Question 58

Viruses that can infect a baby at birth

Answer 58

1) HSV, varicella, CMV (infected birth canal) | 2) Coxsackie B (faecal contamination)

Question 59

Spread of viruses that cause acute respiratory disease

Answer 59

High titres shed for a short period (~1 week). Influenza, rhinovirus

Question 60

Time of peak infectiousness of measles

Answer 60

Prior to onset of rash

Question 61

Places from which viruses can be excreted in faeces

Answer 61

From epithelial cells lining intestinal tract (rotavirus) | From the liver via the bile duct (Hep A)

Question 62

How is HPV spread?

Answer 62

Only from the top layer of infected skin. Transmitted via mechanical contact. Blood from wart has very high viral titre.

Question 63

How is varicella spread?

Answer 63

Shed from virus-filled vesicles. | Can be spread from respiratory tract (aerosolised)

Question 64

Is the measles rash infectious?

Answer 64

No

Question 65

Which viruses are normally spread via blood?

Answer 65

Viruses that result in persistent viremia

Question 66

Why does direct human-human or human-arthropod-human transmission not often occur with arboviruses?

Answer 66

Levels of virus in the blood are too low

Question 67

How is CMV secreted?

Answer 67

Urine, saliva, tears, breast milk, semen, cervical secretions

Question 68

How is EBV spread?

Answer 68

Saliva

Question 69

How is HIV transmitted?

Answer 69

Milk, semen, cervical secretions, blood