Viruses - what they are and pathogenesis Flashcards
attributes of viruses
They can replicate in hours
They replicate to very high numbers
They have error-prone polymerases (particularly RNA polymerases)
Viruses generate a lot of variants. Most of these are unfit, but some are able to escape existing immunity
A wide range of immune responses is needed to deal with them
You can’t possibly have antibodies and T cells against everything you will be exposed to
Two ways that a virus can leave the cell
They can cause lysis – causing damage to host as they leave
Form an envelope from the host membrane to cause budding – non cytopathic
Common virus diseases of man
Influenza Common cold Measles Mumps Chicken pox/Shingles Glandular fever Hepatitis Papillomas (Warts) AIDS Kaposi’s sarcoma
Diseases that may have viral aetiology
Multiple sclerosis Schizophrenia Type I diabetes Myalgic encephalitis (chronic fatigue syndrome) Other cancers (colorectal)
General patterns of viral infection
Acute infection
Latent, reactivating infection
Persistent infection
Acute Infections - a huge spectrum of disease and range of outcomes
Mumps (Paramyxovirus) Measles (Paramyxovirus) Calicivirus (Norwalk-like) Rotavirus (Reoviridae) Poliovirus (Picornaviridae, enterovirus) SARS (Coronavirus) Ebola Smallpox Colds (rhinovirus) Flu
Latent/reactivating infections - Human Herpes Viruses
Herpes simplex virus type 1 Herpes simplex virus type 2 Varicella zoster virus (3) Epstein-Barr virus (4) - glandular fever, kissing disease Cytomegalovirus (5) Human herpesvirus 6 Human herpesvirus 7 Human herpesvirus 8
Life-long infection, controlled by immunity
Herpes simplex virus type 1
Primary Gingivostomatitis as a child
Cold Sore when you are older and immune system is weak
Varicella zoster virus (3)
chickenpox as a child
possible shingles during reactivation as an adult, appears in very defined sectors
Herpes Simplex & VZV latency
Retrograde axonal transport involving microtubules to neuronal nucleus
These viruses have ways to evade the immune system, they will hide in dorsal ganglion and go into latency not presenting antigens to present to your immune system.
Common trigger of cold sore is immunosuppression event, older people get shingles because if immunosuppression, it goes back down the nerve, it affects the area that is innervated by that dorsal root ganglia
Persistent Infections in the absence of an active immune response
First, a virus that gets in to an animal to cause immunotolerance where it doesn’t cause an immune response
HIV - retrovirus
HCV - flavivirus
Get a peristent virus that is controlled by the immune system
Bovine Viral Diarrhoea Virus
Usually a classical acute infection; makes the animals sick and immunosuppressed for a couple of weeks; symptoms very much like foot-and-mouth
Virus can be spread by aerosols and faeces
Reservoir of virus is a small pool of persistently infected animal.
These animals acquire the virus as foetuses before the development of the adaptive immune response, in a largely asymptomatic infection.
These animals see the virus as self!
These animals constantly shed the virus.
Eventually the virus in these animals mutates and generates a cytopathic virus that kills the animal because they do not see the virus as foreign.
How does virus infection of a host lead to disease?
Many infections are apathogenic 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 results from cell tissue damage cause by viral infection usually lysis of cell - caused by cytopathic viruses
Cytopathic damage: EBOLA targets Vascular Endothelial Cells
Ebola targets endothelial cells
The receptor is only on endothelial cells hence why affects it only
Causes lysis of them
Therefore causes massive blood vessel leakage, blood in the skin and organs -> organ failure
Cytopathic damage: Influenza A virus targets lung epithelia
Lack of cilia - inabillity to effectively clear infection
Cytopathic damage: RSV induces syncytia in lung epithelia
Longterm tissue damage in kids, associated with asthma
Cytopathic effect meaning?
structural changes in host cells that are caused by viral invasion
How does virus infection of a host lead to disease?
On some occasions the relative limited damage caused by the virus is made worse or even caused by the host’s immune system (= immunopathology).
Immunopathology - Hepatitis C Virus (HCV)
Chronic hepatitis is a disease of severe Liver damage and loss of hepatocytes – caused by persistent HCV infection
Hepatitis associated with extensive liver infiltration of leukocytes - pro-inflammatory cytokine levels very high
HCV persistence is associated with a lack of CD8+ cells - viral clearance and disease is associated with generation and infiltration of CD8+ cells. The CD8 cells attack the infected liver cells.
Hep C does not grow well in hepatocytes – but still causes damage due to immune response to the liver
Immunopathology - Cytomegalovirus (CMV)
Infants infected with cytomegalovirus have circulating immune complexes that are deposited in the kidneys and joints resulting in pathology such as arthritis and glomerular nephritis.
Immunopathology - Dengue Virus Infections
Dengue virus infection is the most common mosquito-borne infection worldwide–even surpassing malaria.
There are 4 serotypes (1–4), all of which have the same clinical manifestations.
- 5 billion people at risk of dengue due to living in an endemic area, in addition to the actual living conditions.
- 50–100 million infections per year
- 500,000 hospitalizations due to severe disease.
Case fatality rate close to 5%
-risk of fatal disease is <1% with appropriate therapy
-Dengue fever and severe dengue
Dengue fever
- malaise (discomfort)
- high fever
- headache
- generalised arthralgia (pain in a joint)
- myalgia (muscle pain)
Severe dengue, which may include dengue shock syndrome (DSS), and hemorrhage.
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. In fact 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.
problem with viruses and immunity?
Viruses are Intracellular Pathogens (they are only outside of a host cell whilst spreading to new cells)
Viruses can replicate very quickly
Viruses are small and do not have cell walls with obvious PAMPs
