Mechanism of Viral Infection and Pathogenesis Flashcards
Why do most viruses we come across not infect us?
Most of these don’t “infect” us:
- They are adapted to non-human hosts
- They are excluded by surface barriers
- Innate Immunity prevents them establishing
- Adaptive immune response has seen something similar
What are the different sites of microbe entry?
- Conjunctiva
- Respiratory tract
- Arthropod bite
- Capillary
- Scratch injury
- Skin
- Anus
- Urogenital tract
- Alimentary tract
Name common viruses causing disease in humans
> Smallpox and (almost) Poliomyelitis are eradicated through vaccination
- Influenza
- Common cold
- Measles
- Mumps
- Chicken pox/Shingles
- Glandular fever
- Hepatitis
- Papillomas (Warts)
- AIDS
- Kaposi’s sarcoma
- COVID-19?
What are the 3 general patterns of viral infection?
- Acute infection
- Latent, reactivating infection
- Persistent infection
What is the virus load?
Virus load: viral replication - virus detected in us
What happens during acute infection?
The virus load gets cleared by the immune response or else we die
Disease symptoms occupy when virus load is at its highest but generally recover and develop long-lasting immunity
Name common acute viral infections
- common cold
- measles
- ebola lesion
- smallpox
Outline the pattern of infection of common cold
The virus remains in upper respiratory tract and nose and sore throat - easily resolved
How does measles present?
There are typical spots and ulceration of tongue - difficulty eating, as well as CNS problems
Describe the effects of an ebola lesion
A complete destruction of endothelium, massive haemorrhage - bleed to death; poorly resolved
Describe the pathogenicity of influenza
different strains produce a huge range of outcomes
e.g. 1918 vs 2005
Describe the 2005 influenza strain
2005 strain: circulating seasonal strain didn’t compromise people’s health greatly - similar to common cold
Describe the 1918 influenza strain
1918 strain: highly pathogenic strain with high fatality rate (great pandemic)
What causes chronic viral infections?
Virus persists throughout life, immune system responsible for keeping it under control
What is a latent reactivating infection?
Burst of viral replication and disease controlled by immune system to become disease free
However episodic reactivations of virus occur dut reservoir in host still present - mediated by immune system
What causes reactivation of a viral infection?
If immune system breaks down by the smallest degree the virus can be reactivated causing disease symptoms
Outline the various human herpes viruses
- Herpes simplex virus type 1
- Herpes simplex virus type 2
- Varicella Zoster virus
- Epstein-Barr virus
- Cytomegalovirus
- Human Herpes virus 6
- Human Herpes virus 7
- Human Herpes virus 8
Describe the structures of all 8 herpes viruses
All related viruses containing large dsDNA genomes - highly specific
What is the consequence of herpes virus infection?
lifelong infection, controlled by immunity
What are the effects of Herpes simplex virus HHV1?
Primary gingivostomatitis & cold sores
Primary facial rash (spotty) and causes temperature for ~1 day and then symptoms resolve
But the virus remains and at various points in life when under immune stress, produces cold sores
Which herpes viruses are responsible are similar to chicken pox HHV3?
Varicella Zoster Virus (VZV)
Shingles
What is the effect of HHV3?
Disseminated rash and pock marks, symptoms worsen the later in life you acquire the infection
Why is HHV3 reactivation worse than other herpes viruses?
Many years later after immune system wanes, it can reactivate same virus to cause highly septic, painful, blistering infections
Describe the mechanism of primary infections in herpes virus
During primary infection, these viruses give very specific fevers e,g.
- Disseminated rash in Herpes Simplex
- Delocalised rash in Chickenpox
How do herpes viruses become latent?
In both cases, the virus’ travel up neurons of dorsal root ganglion where they establish a persistent infection
→ largely switched off by immune system
What causes reactivation of the herpes viruses and their effects?
Secondary stimulus (immunosuppression) causes virus to burst out and travel back down from neurons to produce local infections
- Cold sores
- Rash
Describe the pattern of persistent infections
Virus peaks but doesn’t fully resolve
Don’t see disease symptoms for relatively long time but then a big eruption occurs e.g. HIV
What is the significance of rubella in pregnant women?
Rubella infection during pregnancy can cause unborn foetus to also develop rubella in its tissues
What are the effects of rubella on foetus’?
If early enough (1st trimester); immune system doesn’t recognise virus as foreign (sees as self) ∴child is immunotolerant
- virus tears through neonatal tissues to cause congenital rubella
- Not immunity controlled
Outline examples of persistent infections
HIV: virus infects CD4+ cells and weakens immune system
HCV: virus infects hepatocytes and damages liver
Congenital rubella: in utero infection seen as self - damages neonatal tissues
What are inapparent infections?
Many infections are apathogenic or associated with relatively mild symptoms
What makes a virus successful?
A successful virus is one that replicates well enough to spread to the next host
What are the requirements for an inapparent virus to thrive?
Requires that viruses be non-cytopathic and host-adapted
Describe the pathogenesis of cytopathic viral infections
Infections causing tissue damage are often resolved v. quickly (flagged rapidly by immune response) or immune response not quick enough causing death
How does ebola cause cytopathic damage?
EBOLA targets vascular endothelial cells
Describe the structure and function of ebola virus
EBOLA virus has very strange specific shape that only targets receptors vascular endothelial cells
What happens to ebola infected cells?
Infected cells undergo lytic damage by the ebola virus replicating in blood vessels
How does influenza A cause cytopathic damage?
Influenza A Virus targets lung epithelia and destroys the cilia to prevent its removal
What is the role of cilia in the respiratory tract?
Respiratory epithelium lined by cilia to expel mucus trapping dust, pathogens etc.
What are the effects of respiratory syncytial virus (RSV)?
Respiratory Syncytial Virus induces syncytia in lung epithelia
Associated with development of atopic life-long asthma
What is the cytopathic effect of RSV?
At site of RSV infection, cells are fused together to form a heterokaryon (lots of nuclei inside one cell) - non-functional
What is immunopathology?
When the relatively limited damage caused by the virus is made worse or even caused by host’s immune system
Give an example of immunopathogenic viruses
Hepatitis C
What are the initial effects of Hepatitis C?
Begins with classical acute infection
~20% permanently cured early on
Describe the progression of hep C infection
80% progress to chronic liver inflammation which continues to become fibrotic liver and eventually severe liver damage / cirrhosis or even hepatic cancer
How does Hep. C become immunopathogenic?
HCV: non cytopathic but is broken down and peptides from the virus are presented to MHC Class I molecules
What is chronic hepatitis?
Chronic hepatitis is a disease of severe liver damage and loss of hepatocytes = caused by persistent HCV infection
How does the immune system respond to chronic HCV?
Hepatitis associated with extensive liver infiltration of leukocytes
Pro-inflammatory cytokine levels are very high in liver
Which immune cells are responsible for HCV clearance?
Viral clearance and disease is associated with generation and infiltration of CD8+ cells which attack infected cells and destroy them
How does HCV become persistent?
HCV persistence is associated with generation of HCV variants that aren’t recognised by CD8- cells
What is dengue virus?
Dengue virus infection is most common mosquito-borne infection worldwide surpasses malaria
Outline the epidemiology of dengue virus
- 2.5bn people at risk of dengue due to living in endemic areas
- Estimated 50-100 million infections per year and 500,000 hospitalisation due to severe disease
- Case fatality rate from severe damage is 1 - 5%
How many types of dengue virus are there?
There are 4 serotypes (1-4) all of which have the same clinical manifestations
How does infection from different dengue serotypes affect immunity?
Infection from one serotype is usually resolved after suffering mild symptoms. However a heterotypic infection from a different strain would cause more serious symptoms due to a phenomenon known as antibody-dependent enhancement (ADE)
What are the severe effects of dengue virus?
Severe dengue, may include dengue shock syndrome (DSS) and haemorrhage
Greatest risk is previous infection with different serotype
How does ADE (antibody-dependent enhancement) worsen Dengue virus?
- Non-neutralising antibodies coat virus
- Form immune complexes which get internalised into mononuclear phagocytes through Fc receptors
- Fixation of complement by circulating immune complexes
- Causes release of products of complement cascade
- Sudden increased vascular permeability
- Shock and death
Who is affected by influenza virus?
People of all ages are infected, usually only a serious problem in old people/children with asthma
Describe the pathogenesis of Influenza virus
- Mild URTI 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
How does influenza virus effect immunity?
Infection generates powerful,life-long immunity
Easy to vaccinate against if you know what’s coming
Why is a new vaccine produced for influenza each year?
Exposed to flu every year
Undergoes antigenic shift to produce new strains of virus
What does viral infection outcome depend on?
- What you’re infected by
- Route of infection
- Whether you’ve seen it (or anything similar) before
- State of your immune system
