Mechanism of viral infection and pathogenesis Flashcards
Why do most viruses not infect us like those found in seawater?
- They are adapted to non-human hosts
- They are excluded by surface barriers (e.g. skin)
- Innate Immunity prevents them establishing
- Our adaptive immune response has seen something similar
What two key factors affect the disease outcome from a virus?
- Route of entry
- Tissue specifity
State the different general patterns of viral infection (4) and draw the graph of each virus load and disease symptoms? VD
- Acute infection
- Chronic infection (timecourse is long or for life):
- Latent, reactivating infection
- Persistent infection: 1. Chronic (very last one), 2. Latent
- Virus load = How much of the virus is replicating inside of you
What is acute infections? VD
- Covers a huge spectrum of disease and range of outcomes
- Typically an infection that has limiting life span
- Resolution via immunity (or not)
What is latent, reactivating infection?
- Waves of viral activation + viral inactivation with disease
- Symptoms may not occur
- Life-long infection controlled by immunity
State a key example of latent, reactivating infection?
Human Herpes virus (8 types found within humans - HHV 1-8)
State key symptoms of HHV-1 and HHV-3?
- HHV-1 = Herpes simplex virus: Primary gingivostomatitis, Cold sore
- HHV-3/VZV (Varicella Zoster Virus): Chickenpox, Shingles
Describe latent persistent infection and state and describe 3 key examples?
- Viral levels constantly controlled by active host immunity
- Initial round of viremia followed by low viral load and then end of life eruption in virus.
- Examples:
- HIV - retrovirus
- HCV - flavivirus
- Measles - causes acute infection, but virus shed (dissapears) for several weeks after acute infection, and rare encephalitis cases years after infection
Describe chronic persistent infection and describe a key examples?
- Immune system doesn’t control viral loads, so levels stay high
- Example: Congential Rubella
- If infected in utero, virus is seen as self, baby is born immunotolerant and virus continues to replicate (and cause damage) in neonatal tissues.
Describe the effects of congential rubella?
- Rubella virus viremia can infect the placenta of pregnant women, and viral replication can infect all foetal organs. Causes huge amount of tissue damage
- The hallmark of foetal infection is chronic infection that persists throughout foetal life, with shedding of virus up to 2 years after birth
- Viral shedding by infants with congenital rubella syndrome can result in outbreaks
How viral infections lead to disease
State the 3 keys principles involved in how a viral infection of a host can lead to disease?
- Many infections are pathogenic or associated with relatively mild symptoms; it is important to realize that from the virus’ point of view these are not always failed or resolved infections - a successful virus is one that replicates well enough to spread to the next host
- Pathogenesis (development of disease) results from cell and tissue damage caused by the viral infection. On most occasions the damage is limited by the host’s immune system
- On some occasions the relative limited damage caused by the virus is made worse or even caused by the host’s immune system
(Eimmunopathology)
Describe example of inapparent infections and what qualities of a virus it requires?
- 90% of all poliovirus infections are asymptomatic (inapparent) - no symptoms
- Many of us get infected with parainfluenzavirus 5 without clear symptoms
- Despite the bad PR ‘flu often gives rise to very mild respiratory disease
- Requires that viruses be non-cytopathic and host-adapted
- Non-cytopathic = Doesn’t damage the cell it infects
- Host-adapted = ability of a pathogen to circulate and cause disease in a particular host population.
State the cytopathic damage EBOLA, influenza A and Respiratory
Syncytial Virus (RSV) induces?
- Ebola = Vascular endothelial cells targeted
- IA = Lung epithelial (cilia) targeted
- RSV= Syncytia induced in lung epithelia
- A single cell or cytoplasmic mass containing several nuclei, formed by fusion of cells or by division of nuclei.
- Cells lose function
State 3 examples of diseases that cause immunopathology?
- HCV
- Dengue virus
- RSV
Describe HCV and how immunopathology arises from this?
- Chronic hepatitis is a disease of severe liver damage and loss of hepatocytes - caused by persistent HCV infection
- HCV is non-cytopathic
- Hepatitis associated with extensive liver infiltration of leukocytes
- Pro-inflammatory cytokine levels very high
- Viral clearance and disease is associated with generation and infiltration of CD8+ cells which attack infected cells and destroy them
- HCV persistence is associated with the generation of HCV variants that are not recognised by CD8+ cells
