Acute Viral Infection L20-21

Question 1

Describe Acute infection.

6

Answer 1

• Infection of small number of cells
• Many cycles of multiplication – infection of surrounding cells
• May stay local or spread systemically
• Signs and symptoms of disease
• Clearance of virus by immune response and recovery
  OR
  Latent infection/chronic infection/death
• Short duration – days to weeks

Question 2

Describe Subclinical infection.

3

Answer 2

• Similar course to acute infection, but no signs or symptoms
• Either immune response clears virus before symptoms are apparent
  OR
  Dead cells are replaced quickly enough that symptoms not apparent
• Subclinical infection is the most common result of virus infection

Question 3

Name the disease:

• One of the most contagious diseases known
• Once everyone on population is infected the virus can only spread between young children and infants
• In populations

Answer 3

Measles.

Question 4

Define Pathogenesis.

Answer 4

The manner of development of a disease.

Question 5

Describe the pathogenesis of measles.

7

Answer 5

• Transmission via aerosol droplets
• Virus replicates in epithelium of upper respiratory tract
• Primary viraemia (little free virus in blood – mostly associated with lymphocytes and macrophage)
• Virus replicates in lymphoid tissue (spleen, lymph nodes, appendix, tonsils)
• Secondary viraemia
• Virus spreads to other organs (incl. skin, conjunctiva, liver, kidney, lung, gut)
• Characteristic rash develops

Question 6

List the symptoms of measles.

5

Answer 6

• Fever
• Respiratory tract symptoms: runny nose (coryza) and cough
• Koplik’s spots
• Conjunctivitis
• Maculopapular rash: begins on face and extends to the extremities

Question 7

The Paramyxoviridae:

• Transmit readily via the respiratory route
• 2 patterns of infection and disease in humans: DESCRIBE THEM.

Answer 7

1. Localised acute infections of the respiratory tract trivial in healthy adults but causing potentially dangerous disease on primary infection of infants and children.
   - eg. Respiratory Syncytial Virus (RSV), human Metapneumovirus (hMPV)
2. Systemic acute infection, initiated in the respiratory tract
   vary widely in severity.
   - eg. Measles, mumps.

Question 8

True or false? Paramyxoviruses induce fusion of infected cells.

Answer 8

True.

Question 9

Describe the Entry phase of a measles infection.

Answer 9

H protein docks with cellular receptor (CD150/SLAM).
Induces structural change in F protein ——–> FUSION.
RNP is released into cytoplasm.

Question 10

Describe the Transcription phase of a measles infection.

Answer 10

Genome is transcribed by RdRp into 6 mRNA’s – gradient of transcripts.

Question 11

Describe the Replication phase of a measles infection.

Answer 11

Genome is transcribed by RdRp into full length +ve sense copy of genome.
-ve sense genomes are copied by RdRp from full length +ve sense templates and associate with N, P and L proteins to form new RNPs.

Question 12

Describe the Assembly and release phase of a measles infection.

Answer 12

F & H proteins move from Golgi to cell membrane.

M protein associates with cytoplasmic domain of F&H and with the –ve RNP.

Question 13

T cell response, rather than antibody response, is important in clearing measles virus.

How do we know?

Answer 13

• Agammaglobulinaemic children (no IgG) recover normally from infection
• Children with T cell deficiencies fail to clear virus leading to progressive illness and death.

Question 14

True or false? Most measles symptoms are caused by the immune response to the virus, rather than cytopathic effect of virus.

Answer 14

True.

Question 15

How do cytokines secreted by infected cells & macrophage induce a fever?

Answer 15

By triggering hypothalamus to increase body temperature.

Question 16

How do cytokines secreted by infected cells & macrophage induce coryza?

Answer 16

By increasing vascular permeability which in turn increases nasal secretion.

Question 17

What causes a rash?

Answer 17

Result of cytotoxic T cells attacking infected endothelial cells in capillaries. Also damage to endothelial cells caused by deposition of antigen-antibody complexes.

Question 18

Why is not having a rash in measles a bad thing?

Answer 18

It indicates a poor T cell response.

Question 19

Describe Giant cell pneumonia.

Complication of measles

Answer 19

• Impaired T cell response (often indicated by no rash)- extensive viral replication in lungs – leading to syncitium formation and pneumonia.
• Rare but often fatal.

Question 20

Describe a secondary bacterial infection.

Complication of measles

Answer 20

Measles infection is immunosupressive and predisposes to secondary bacterial infection, typically otitis media (ear infection) and pneumonia (~15% of cases).

Question 21

What proportion of the fatalities are caused by pneumonia as a complication of measles?

Answer 21

60%.

Question 22

Describe Encephalitis.

Complication of measles

Answer 22

• 1:1000 cases

- 90% survival but may have neural damage (eg deafness, seizures)

Question 23

Describe Sub-acute sclerosing panencephaliltis (SSPE).

7

Answer 23

• Very rare, 1:10^5 - 1:10^6
• Slow progressive, fatal disease of CNS
• Risk factors: male, measles at <2yrs
• Develops 1-10 years after infection
• Persistent brain infection leads to hyperimmune antibody response – extremely high levels of neutralising antibody in serum and CSF (10x concentrations found in acute infection)
• Defective (non-infectious) virus particles present in brain tissue.
• Sequence of genome isolated from brain indicates that the viral strain is related to the original infecting strain (ie. disease is unlikely to be caused by reinfection)

Question 24

How many strains of measles are there?

Answer 24

1.

Question 25

What type of vaccine is the measles vaccine?

Answer 25

Live attenuated vaccine.

Question 26

Name virus type:

• Filamentous morphology
• Highly pleomorphic (adopt different shapes)
• Cause severe haemorrhagic fever
• 1967: Marburg virus
• 1976: Ebola virus

Answer 26

Filoviruses.

Question 27

Name the virus:

• Four subtypes:
  Zaïre, Sudan, Côte d’Ivoire and Reston (asymptomatic).
• Transmitted by direct contact with the bodily fluids of infected persons
• First identified in Zaire in 1976
• 1,850 cases with over 1,200 deaths have since been documented
• One of most infectious and deadly viruses – 50-90% mortality

Answer 27

Ebola virus.

Question 28

Describe the symptoms of Ebola virus.

Answer 28

• Non-specific flu-like symptoms – headache, fever, aches & pains
• Diarrhoea & vomiting
• Maculopapular rash in ~50% patients around day 5-7
• Severe bleeding – especially gastrointestinal – in proportion of patients

Question 29

Describe how Ebola virus is treated.

Answer 29

• Replacing fluid
• No vaccine
• Containment is critical - barrier nursing - quarantine

Question 30

What is the suspected primary reservoir of the Ebola virus?

Answer 30

Fruit bats.

Question 31

Describe the structure of the Ebola virus.

3

Answer 31

• Enveloped
• Helical nucleocapsid
• -ve ssRNA genome

Question 32

Which 2 virus types are filoviruses closely related to?

Answer 32

• Rhabdoviruses (eg rabies)

- Paramyxoviruses (eg measles)

Question 33

True or false? There is only 1 identified receptor on cells for filoviruses.

Answer 33

False. Several different receptors have been identified.

Question 34

Which cells do filoviruses initially infect?

Answer 34

• Monocytes
• Dendritic cells
• Macrophages
• Endothelial cells

Question 35

What do filoviruses suppress during infection?

Answer 35

• Production of IFNa and b in infected cells
• Action of IFNa and IFNb
• Maturation of dendritic cells
• Suppresses activation of T cells and B cells thus suppresses adaptive immune response