Mechanism of viral infection and pathogenesis Flashcards
What are sites of microbe entry?
○ Conjunctiva ○ Respiratory tract ○ Scratch/injury ○ Alimentary tract ○ Urogenital tract ○ Skin ○ Anus ○ Capillary
What are the general patterns of viral infection?
- Acute infections
- Chronic infections
- Latent/reactivating infections
What do you generally develop after acute infections?
○ Generally develop long-lasting immunity against these diseases
What happens to virus in chronic infections?
○ Virus persists throughout life and so must be kept under control
What is there a burst of in chronic infections and what happens throughout life?
○ Burst of viral replication
▪ Immune system brings this under control so you are disease free
▪ Throughout your life there are episodic reactivations of the virus as the virus has not been destroyed
§ Can get disease symptoms returning
What is an example of a latent/reactivating infections?
○ Human Herpes Viruses
§ Life-long infection
What is the human herpes virus controlled by?
Controlled by immunity
What are the symptoms of herpes simplex virus(HHV-1)?
▪ Primary gingivostomatitis
What do the symptoms of herpes simplex virus(HHV-1) come back as in times of stress when the virus is reactivated?
▪ Comes back later as a cold sore in times of stress when virus is reactivated
What does the chickenpox(HHV-3) virus symptoms come back as when the virus is reactivated?
▪ Comes back as the shingles when virus is reactivated
Why is HIV a persistent infection?
▪ HIV: virus infects CD4+ cells and weakens immune system
Why is HCV a persistent infection?
▪ HCV: virus infects hepatocytes and damages liver
What happens if congenital rubella is infected in utero and what damage does this cause?
If infected in utero, virus is seen as self, baby is born immunotolerant and virus continues to replicate and cause damage in neonatal tissues
What does herpes give during a primary infection?
○ During a primary infection, herpes gives you very specific fevers
What does the herpes simplex virus give in children?
○ Disseminated rash (herpes simplex virus) in the child
What virus causes chickenpox and what is it?
○ Chickenpox (varicella virus) are a delocalised rash all over the body
In both the herpes simplex virus and varicella virus, where do the viruses travel and what does a secondary stimulus cause?
○ In both these cases, both the viruses travel up neurons and establish a persistent infection where the virus is switched off
§ Secondary stimulus causes them to travel back down the neuron and cause infection locally i.e. cold sore/rash
What defines a successful virus?
○ A successful virus is one that replicates well enough to spread to the next host
What does pathogenesis result from?
○ Pathogenesis results from cell and tissue damage caused by the viral infection
What does tissue damage cause the release of?
○ Tissue damage causes release of viral debris and the immune system is primed
Example of an inapparent infection
○ 90% of all polio virus infections in unvaccinated individuals are asymptomatic (inapparent)
What do many people get infected without celar symptoms of and what is a symptom that is presented?
○ Many of us get infected with parainfluenzavirus 5 without clear symptoms
§ Presents with normal cough
What diseases are known to cause cytopathic damage?
Ebola
What does ebola target and what receptors does it bind to?
○ Ebola targets vascular endothelial cells
§ Binds to receptors that are only expressed on vascular endothelia
What does the influenza virus target?
○ Influenza virus targets lung epithelia
What does RSV induce in lung epithelia?
○ RSV induces syncytia in lung epithelia
What is chronic hepatitis a disease of and caused by what infection?
○ Chronic hepatitis is a disease of severe liver damage and loss of hepatocytes – caused by persistent HCV infection
Can you be vaccinated for chronic hepatitis?
Cannot be vaccinated against this disease
Why does HCV cause disease, despite it being non-cytopathic and hence why does the patient die?
○ If non-cytopathic, it should not cause disease but it does because:
▪ Although the virus causes no damage to the cell its infected, it is broken down by normal function of immune system
▪ Peptides from the virus get presented on surface of hepatocytes through MHC class I
▪ Signals to the immune system that there is a foreign body so immune system attacks
▪ Liver gets full with inflammatory response cells (pro-inflammatory cytokines, leukocytes) which will attempt to clear the infected cells
▪ T cells (CD8 cytotoxic cells) will destroy infected cells
§ So you die because you destroy your own liver
What does HCV start by causing?
HCV starts by causing a classical acute infection
What is hepatitis associated with?
○ Hepatitis associated with extensive liver infiltration of leukocytes
What happens to the levels of pro-inflammatory cytokine in hepatitis?
○ Pro-inflammatory cytokine levels very high
What is viral clearance and disease associated with?
○ Viral clearance and disease is associated with generation and infiltration of CD8+ cells which attack infected cells and destroy them
What is HCV persistence associated with?
HCV persistence is associated with the generation of HCV variants that are not recognised by CD8+ cells
What is the most common mosquito-borne infection?
Dengue Fever
What are the symptoms of a primary infection of dengue fever?
○ Mild fever ○ Skin rash ○ Headache ○ Bone and muscle pain ○ Nausea ○ Vomiting
What are the symptoms of secondary heterotypic infection of dengue fever?
○ Acute fever ○ Severe abdominal pain ○ Headache ○ Plasma leakage ○ Intravascular volume ○ Depletion ○ Coagulation and dysfunction – can bleed out
Why can antibodies formed in response to a dengue infection result in more severe disease and what is this known as?
○ Antibodies formed in response to a dengue infection are not cross-protective against other subtypes of the virus (i.e. protection against dengue virus 1 will not protect you against any other strains)
§ In fact they may result in more severe disease due to a phenomenon known as antibody-dependent enhancement or ADE
What do non-neutralizing antibodies do and what does this result in?
○ Non-neutralizing antibodies coat virus, forming immune complexes
▪ These get internalised into mononuclear phagocytes through their Fc receptors; fixation of complement by circulating immune complexes
▪ This results in release of products of the complement cascade leading to sudden increased vascular permeability, shock and death
What is the pathology of influenza?
○ Mild URTI (upper respiratory tract infection) to severe LRTI
○ Lower respiratory tract infection causing damage to lung epithelia and viral pneumonia, often secondary pneumonia
○ Fever, often prolonged
○ Neurological (headache, malaise)
○ Myalgia
