Acute Viral Infection L20-21 Flashcards
Describe Acute infection.
6
- 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
Describe Subclinical infection.
3
- 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
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
Measles.
Define Pathogenesis.
The manner of development of a disease.
Describe the pathogenesis of measles.
7
- 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
List the symptoms of measles.
5
- Fever
- Respiratory tract symptoms: runny nose (coryza) and cough
- Koplik’s spots
- Conjunctivitis
- Maculopapular rash: begins on face and extends to the extremities
The Paramyxoviridae:
- Transmit readily via the respiratory route
- 2 patterns of infection and disease in humans: DESCRIBE THEM.
- 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) - Systemic acute infection, initiated in the respiratory tract
vary widely in severity.
- eg. Measles, mumps.
True or false? Paramyxoviruses induce fusion of infected cells.
True.
Describe the Entry phase of a measles infection.
H protein docks with cellular receptor (CD150/SLAM).
Induces structural change in F protein ——–> FUSION.
RNP is released into cytoplasm.
Describe the Transcription phase of a measles infection.
Genome is transcribed by RdRp into 6 mRNA’s – gradient of transcripts.
Describe the Replication phase of a measles infection.
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.
Describe the Assembly and release phase of a measles infection.
F & H proteins move from Golgi to cell membrane.
M protein associates with cytoplasmic domain of F&H and with the –ve RNP.
T cell response, rather than antibody response, is important in clearing measles virus.
How do we know?
- Agammaglobulinaemic children (no IgG) recover normally from infection
- Children with T cell deficiencies fail to clear virus leading to progressive illness and death.
True or false? Most measles symptoms are caused by the immune response to the virus, rather than cytopathic effect of virus.
True.
How do cytokines secreted by infected cells & macrophage induce a fever?
By triggering hypothalamus to increase body temperature.
How do cytokines secreted by infected cells & macrophage induce coryza?
By increasing vascular permeability which in turn increases nasal secretion.
What causes a rash?
Result of cytotoxic T cells attacking infected endothelial cells in capillaries. Also damage to endothelial cells caused by deposition of antigen-antibody complexes.
Why is not having a rash in measles a bad thing?
It indicates a poor T cell response.
Describe Giant cell pneumonia.
Complication of measles
- Impaired T cell response (often indicated by no rash)- extensive viral replication in lungs – leading to syncitium formation and pneumonia.
- Rare but often fatal.
Describe a secondary bacterial infection.
Complication of measles
Measles infection is immunosupressive and predisposes to secondary bacterial infection, typically otitis media (ear infection) and pneumonia (~15% of cases).
What proportion of the fatalities are caused by pneumonia as a complication of measles?
60%.
Describe Encephalitis.
Complication of measles
- 1:1000 cases
- 90% survival but may have neural damage (eg deafness, seizures)
Describe Sub-acute sclerosing panencephaliltis (SSPE).
7
- 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)
How many strains of measles are there?
1.
What type of vaccine is the measles vaccine?
Live attenuated vaccine.
Name virus type:
- Filamentous morphology
- Highly pleomorphic (adopt different shapes)
- Cause severe haemorrhagic fever
- 1967: Marburg virus
- 1976: Ebola virus
Filoviruses.
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
Ebola virus.
Describe the symptoms of Ebola virus.
- 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
Describe how Ebola virus is treated.
- Replacing fluid
- No vaccine
- Containment is critical - barrier nursing - quarantine
What is the suspected primary reservoir of the Ebola virus?
Fruit bats.
Describe the structure of the Ebola virus.
3
- Enveloped
- Helical nucleocapsid
- -ve ssRNA genome
Which 2 virus types are filoviruses closely related to?
- Rhabdoviruses (eg rabies)
- Paramyxoviruses (eg measles)
True or false? There is only 1 identified receptor on cells for filoviruses.
False. Several different receptors have been identified.
Which cells do filoviruses initially infect?
- Monocytes
- Dendritic cells
- Macrophages
- Endothelial cells
What do filoviruses suppress during infection?
- 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
