Patterns of Viral Infection Flashcards
What is pathogenesis?
Is the complex interaction between virus and host that results in disease
What is pathogenicity?
A comparison of the severity of disease caused by different microorganisms
What is virulence?
A comparison of the severity of disease caused by different strains of the same microorganism
What are the 2 components of pathogenicity in viruses?
Effects of viral replication on the host
Effects of host response on virus and host
What are the fundamental questions of pathogenesis in regards to viral infections?
How does a virion enter the host?
How does it overcome local defences?
How does it spread to other areas of the body?
How does it exit from the host to infect other susceptible hosts?
Why is one viral strain more virulent than another?
Replication rate
Tropism
Ability to evade host immune defences
Changes in ability to disseminate within the host
How can virulence change?
Very small changes in the viral genome (eg influenza B can change to bind to human entry protein as well)
What cellular factors determine pathogenicity of viruses?
Presence of receptors for binding
Physical and molecular environment of host cell must enable initial replication cycle (eg upper respiratory viruses may ideally want 33 degrees cells)
What is the cytopathic effect?
Many viruses kill the cells in which they replicate. Infections induce characteristic appearance.
What can CPE be used for?
Diagnosis of infecting virus
How can viruses enter host through the skin?
Through abrasians
Entry via inoculation with contaminated needles
Through insect or animal bites
How can viruses enter host through mucous membrane?
Entry via respiratory tract
Entry via GI tract (faecal-oral route, eg poliovirus causing poliomyelitis)
Entry via conjunctiva (Enterovirus type 70 causes conjunctiva)
Entry via genital tract (eg. STIs)
How do viral infections of the respiratory tract manifest themselves?
Could show symptoms above the neck and below the neck.
How do viruses spread?
Through blood (either through capillaries by replicating in endothelial cells or through insect bite)
Through lymphatic capillaries they can enter circulation as well
What is viraemia?
Presence of infectious virus in the blood
What causes active viremia vs passive viremia?
Virus replication causes active
Virus introduction causes passive
What is primary viremia?
Virus enters blood after initial replication at site of entry
What is secondary viremia?
Virus produced by disseminated infections
How is there diagnostic value in viremia?
The secondary viremia is stronger allowing blood samples to give us more information
What are the important target organs for viral infections?
Skin
Lungs
Liver
Kidneys
CNS
What do viral infections of the skin typically look like?
A skin rash or exanthem
Vesicular erutions caused by replication of viruses in epthelial cells
Maculopapular rash (destruction of cells by Cytotoxic T Lymphocytes)
Purpuric rash causing haemorrhaging (as seen in dengue virus)
What type of infections hit the lungs?
Most respiratory infections are localized
Some are part of a generalized infection (e.g. Measles –
pneumonitis is a common feature)
What type of infections hits the liver?
Hepatitis viruses
Also infected during generalized infections like yellow fever
What type of infections affect the kidneys?
Rarely infected: CMV infects proximal renal tubules; hantaviruses cause haemorrhagic fever with nephritis
How is CNS reached by viruses?
Access from bloodstream during viremia via nerves in periphery connected to CNS
Is neural spread characteristic of all viral infections?
Only for some like rabies, herpes simplex and varicella zoster.
For others it is an infrequent diversion from normal actions
What is a neurotropic virus?
A virus that can infect neural cells
What is a neuroinvasive virus?
Virus that can enter CNS after infection of a peripheral site
What is a neurovirulent virus?
A virus that can cause disease in nervous tissue
Why don’t all viruses get transmitted as easily as influenza?
The reproduction number (Ro) (average number of secondary cases generated by one primary case)
Rank the following from lowest Ro to highest Ro:
Smallpox
SARS
Influenza
Measles
Ro of SARS and smallpox is about 2
Influenza 4
Measles 10
What kind of viruses can create significant public health problems?
Viruses with short incubation periods and high Ro’s
Viruses with long incubation periods are also of serious concern due to viral shedding
What kind of course does an acute infections often have?
A quick peak followed by complete recovery soon after
What kind of course does a persistent viral infection have?
Can have 3 courses:
Smoldering (increases then remains the same for a long time until death)
Latent (comes and goes)
Slow (comes on once and then goes and then comes back to near time of death)
What is the incubation period?
Period between infection and before characteristic symptoms of disease are apparent
What are the normal steps of an acute viral infection?
Rapid onset with shory but severe course
Disease recovers over a period of days
Rapid production of virions followed by resolution of infection by immune system of the host
What is the prodromal period?
The period just before symptoms of illness start to show
What is happening during incubation period?
Viral replication and host response but not at a noticeable level
What causes most symptoms of viral infections?
The host immune system
Why do acute infections often present common public health problems?
Often associated with serious epidemic affecting millions of people
Infected host is often infectious before symptoms manifest
Infections hard to control in large populations
Effective antivirals require early action which is rarely the case
How does measles virus typically present?
Fever >38 degrees
Respiratory problems (coryza cough)
Conjunctivitis
Koplik’s spots
Rash (3 - 5 days after onset of symptoms)
What is subacute sclerosing panencephalitis?
A complication of measles which presents after 6 - 10 years of initial infection
What happens in subacute sclerosing panencephalitis?
It is a persistent infection of the CNS.
Neurons and oligodendrosites contain measles virus exclusion bodies. This triggers extensive mononuclear inflammation including CD4+ and CD8+ T cells as well as monocytes and antibody secreting B cells. The immune cells are unable to clear MeV infection from the brain.
It is unknown whether the cause of death in this condition is the MeV infection or immune response
In who does MeV + SSPE typically happen?
If primary infection occurred before 2 years of age
What are persistent viral infections?
Virions, genomes, proteins are produced or persist for long periods,
often for lifetime of host
Can viral genomes persist in absence of viral proteins?
Yes they can persist in host genomes
What are the types of persistent infections?
– Chronic: virus is always detectable
– Latent: virus sequesters in a tissue with recrudescence
How is hep B transmitted?
Exposure to blood + blood products
Childbirth
Transfusion
Sex
Contaminated needles
Nosocomial infections
What is the main target cell for hep B?
Hepatocytes
What is the result of persistent hepB virus?
Cirrhosis and development of hepatocellular carcinoma
What is the estimated number of hepB carriers?
350million
How does hepB virus (HBV) persist?
In the nucleus of infected hepatocytes as covalently closed circles of DNA. HBV cccDNA may be reactivated and allow virus to replicate.
HBV includes a reverse transcriptase enzyme which enables antiretroviral drugs developed for HIV to be used to work on HBV.
How does age affect the carrier risk of HBV?
The older you are the less likely you are to suffer from chronic HBV.
What is herpesvirus infection like?
A latent infection following a primary infection.
What happens after primary herpesvirus infection?
Viral genome sits in the host and is reactivated in response to certain stimuli
What stimulates herpesvirus recurrence?
Fever, physical or emotional stress, hormones, menstruation
Where does the herpesvirus replicate in following reactivation?
In the sensory neuron and is transported to site at or near entry
Can herpesvirus cause infection in CNS?
Rarely
Where in the neuron does the herpesvirus lay dormant?
In the cell body of sensory neuron