Medical Microbiology: Mechanism of Viral Infection and Pathogenesis Flashcards
Why don’t most viruses infect humans?
- They are adapted to non-human hosts
- They are excluded by surface barriers e.g. skin and mucosal surfaces
- Innate Immunity prevents them establishing
- Our adaptive immune response has seen something similar
What are some major sites of microbe entry into the human body?
- Conjunctiva
- Respiratory tract
- Alimentary tract
- Urinogenital tract
- Anus
- Skin
- Scratch/injury
- Capillary
- Arthropod
What are some common viral diseases of man?
- Influenza
- Common cold
- Measles
- Mumps
- Chicken pox/shingles
- Glandular fever
- Hepatitis
- Papillomas (warts)
- AIDS
- Kaposi’s sarcoma
- COVID-19?
Describe the pattern of acute viral infection
- Increase in virus load straight after infection
- Virus load cleared by the immune system
- Once virus load cleared symptoms will subside
- Symptoms occur when virus load is at its highest
There are a wide range of diseases and outcomes caused by acute infections. Give some examples of these
- Common cold - Usually resolved by immune system
- Measles - Difficulty in eating, CNS problems
- Ebola - Massive haemorrhaging, usually bleed to death
- Smallpox - High fatality rate
Give an example of the same acute viral infection that caused different symptoms and outcomes
- Influenza strain 2005 - Similar to common cold
- Influenza strain 1918 - Highly pathogenic strain
Describe the pattern of latent reactivating viral infection
- Burst/increase of viral load/replication which leads to disease symptoms
- Viral load cleared by immune system so disease symptoms subside
- However, virus stays within host and so throughout life there are episodic reactivations of the virus
- These result in disease syptoms occuring again
Give an example of a latent reactivating viral infection
- Human herpes viruses
- Large dsDNA genomes
- 8 different strains that can ONLY infect humans (highly specific)
- Once infected you can’t get rid of them but they’re controlled by immunity
Name the 8 different strains of human herpes virus and the different disease’s they cause
- Herpes simplex virus type 1 (HHV-1) - Classic herpes
- Herpes simplex virus type 2 (HHV-2) - Genital herpes
- Varicella zoster virus (HHV-3) - Chicken pox
- Epstein-Barr virus (HHV-4) - Glandular fever
- Cytomegalovirus (HHV-5)
- Human herpesvirus 6 (HHV-6)
- Human herpesvirus 7 (HHV-7)
- Human herpesvirus 8 (HHV-8) - Kaposi’s sarcoma
What symptoms does Herpes simplex virus type 1 (HHV-1) cause?
- Primary Gingivostomatitis (facial rash)
- Temperature
- HHV-1 stays within the body and when suffereing immune stress you get cold sores instead of primary rash
What symptoms does Varicella Zoster virus (HHV-3) cause?
- Develop chickenpox (rash) - usually at early age
- Years later as immune system weakens HHV-3 can reactivate resulting in painful blisters (shingles)
Explain how primary infection, latency and reactivation results in HHV-1 and HHV-3 causing the symptoms that they do in humans
- Human herpes viruses give you very specific fevers and rashes during primary infection
- E.g. HHV-1 gives you localised rash while HHV-3 gives you delocalised rash
- Both HHV-1 and HHV-3 travel up neurons and establish persistant infection where virus is latent (switched off)
- Viruses usually stays latent in sensory neurons in dorsal root ganglion
- Secondary stimulus (usually immunosuppression) causes viruses to travel back down neurons and cause localised reinfection
- Re-infection localised as virus causes it in area of body where neuron it infiltrated travels to
Describe the pattern of persistant viral infections
- Burst in viral load causing disease symptoms
- Immune response then causes large decrease in viral load but virus still present in small quantity for very long time
- After long time there’s another burst in viral load resulting in another peak and disease symptoms
Give some examples of persistant viral infections
- HIV - Infects CD4+ cells and weakens immune system
- HCV (Hepatitis Virus C) - Infects hepatocytes and damages liver
- Congenital Rubella - If infected in-utero, virus seen as self so baby born immunotolerant. Virus continues to replicate (and cause damage) in neonatal tissues
Do most viral infections cause disease in humans? Explain why this is the case
- No, many infections are apathogenic or associated with relatively mild symptoms
- This is because viruses are adapted to be able to replicate without us knowing so that it can spread
- NOTE: Important to realise that asymptomatic infections aren’t infections that have failed as a successful virus is one that replicates well enough to spread to the next host, so doesn’t have to cause symptoms
Give some examples of inapparent (asymptomatic) infections
- Polio: 90% of all poliovirus infections are asymptomatic in non vaccinated people
- Parainfluenza virus 5: Many of us get infected without clear symptoms
- Flu: Often gives rise to very mild respiratory disease
What features does a virus that causes inapparent infections need to have?
- Non-cytopathic - Causes no apparent damage to cells
- Host-adapted - Adapt to environment of host
How does virus infection of a host lead to disease?
- Pathogenesis results from cell and tissue damage caused by the viral infection
- However, on most occasions the damage is limited by the host’s immune system
- If immunse system can’t deal with damage then viral infection. an lead to death
What cytopathic damage does EBOLA cause?
- EBOLA targets and binds to receptor on Vascular Endothelial Cells
- This causes lytic damage whicg results in the vascular endothelial cells being destroyed
What cytopathic damage does Influenza A virus cause?
- Influenza A infects and destroys respiratory epithelial cells making it difficult for cilia on surface of epithelial cells to clear virus
What cytopathic damage does Respiratory Syncytial Virus (RSV) cause?
- RSV induces syncytia in respiratory epithelial cells - causes respiratory epithelial cells to fuse togther to form one large multinucleated cell
On some occasions the relatively limited damage caused by the virus is made worse or even caused by the host’s immune system (immunopathology). Give an example of a viral infection where this is the case
- Hepatitis C
Hepatitis C virus is non-cytopathic so explain how the symptoms of the disease occur?
- Chronic hepatitis is a disease of severe liver damage and loss of hepatocytes – caused by persistent HCV infection
- Infection causes Pro-inflammatory cytokine levels to be very high as well as extensive liver infiltration of leukocytes
- Pro-inflammatory cytokines and Leukocytes attempt to clear virus
- Viral clearance and disease is associated with generation and infiltration of CD8+ cells into liver which attack infected cells and destroy them
- This leads to destruction of hepatocytes
What is Dengue fever?
- Dengue virus infection is the most common mosquito-borne infection worldwide
- Case fatality rate from severe dengue is 1 - 5%
- There are 4 serotypes (1–4), all of which have the same clinical manifestations
What are some symptoms of the primary infection of Dengue virus?
- Mild fever
- Skin rash
- Headache
- Bone and muscle pain
- Nausea
- Vomiting
What are some symptoms of the secondary heterotypic infection of Dengue virus?
- Heterotypic infection -infcetion by a different strain of virus
- Symptoms include:
- Acute fever
- Severe abdominal pain
- Plasma leakage
- Intravascular volume depletion
- Coagulation dysfunction
Dengue Virus is also non-cytopathic so explain how the symptoms of the disease occur?
- Greatest risk is a previous infection with a different serotype
- Antibodies formed in response to a dengue infection are not cross-protective against other subtypes of the virus.
- They may result in more severe disease due to a phenomenon known as antibody-dependent enhancement or ADE
- Non-neutralizing antibodies coat virus, forming immune complexes which get internalised into mononuclear phagocytes through their Fc receptors
- Fixation of complement by circulating immune complexes results in release of products of the complement cascade leading to sudden increased vascular permeability, shock and death
Describe the pathpology of Influenza
- Caues mild Upper respiratory tract infcetion (URTI) to severe Lower tract respiratory infection (LRTI)
- LRTI causes damage to lung epithelia and viral pneumonia, often secondary pneumonia
- Fever, often prolonged
- Neurological effects (headache, malaise)
- Myalgia
How can Immunity to Influenza be produced?
- Infection - Generates powerful, life-long immunity
- Vaccine - Easy to vaccinate against if you know what’s coming
What is antigenic shift and how does it affect the ability to produce a vaccine for a virus?
- Antigenic shift - Virus changes the antigens present on its surface
- Normally vaccines can be produced if scientists compare and predict what strain of a particular virus they think is coming
- However, if a virus undergoes antigenic shift scientists may not be able to predict this new strain of the virus and so they can’t produce a vaccine against it
What does the outcome of an infection depend on?
- What you are you infected by
- The route of infection
- Whether you’ve seen it (or anything like it) before
- The state of your immune system
