Viruses - what they are and pathogenesis Flashcards

1
Q

attributes of viruses

A

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

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2
Q

Two ways that a virus can leave the cell

A

They can cause lysis – causing damage to host as they leave

Form an envelope from the host membrane to cause budding – non cytopathic

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3
Q

Common virus diseases of man

A
Influenza			
Common cold	
Measles				
Mumps
Chicken pox/Shingles
Glandular fever
Hepatitis
Papillomas (Warts)
AIDS
Kaposi’s sarcoma
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4
Q

Diseases that may have viral aetiology

A
Multiple sclerosis
Schizophrenia
Type I diabetes
Myalgic encephalitis (chronic fatigue syndrome)
Other cancers (colorectal)
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5
Q

General patterns of viral infection

A

Acute infection
Latent, reactivating infection
Persistent infection

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6
Q

Acute Infections - a huge spectrum of disease and range of outcomes

A
Mumps (Paramyxovirus)
Measles (Paramyxovirus)
Calicivirus (Norwalk-like) 
Rotavirus (Reoviridae)
Poliovirus (Picornaviridae, enterovirus)
SARS (Coronavirus)
Ebola
Smallpox
Colds (rhinovirus)
Flu
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7
Q

Latent/reactivating infections - Human Herpes Viruses

A
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

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8
Q

Herpes simplex virus type 1

A

Primary Gingivostomatitis as a child

Cold Sore when you are older and immune system is weak

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9
Q

Varicella zoster virus (3)

A

chickenpox as a child

possible shingles during reactivation as an adult, appears in very defined sectors

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10
Q

Herpes Simplex & VZV latency

A

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

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11
Q

Persistent Infections in the absence of an active immune response

A

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

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12
Q

Bovine Viral Diarrhoea Virus

A

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.

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13
Q

How does virus infection of a host lead to disease?

A

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

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14
Q

Cytopathic damage: EBOLA targets Vascular Endothelial Cells

A

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

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15
Q

Cytopathic damage: Influenza A virus targets lung epithelia

A

Lack of cilia - inabillity to effectively clear infection

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16
Q

Cytopathic damage: RSV induces syncytia in lung epithelia

A

Longterm tissue damage in kids, associated with asthma

17
Q

Cytopathic effect meaning?

A

structural changes in host cells that are caused by viral invasion

18
Q

How does virus infection of a host lead to disease?

A

On some occasions the relative limited damage caused by the virus is made worse or even caused by the host’s immune system (= immunopathology).

19
Q

Immunopathology - Hepatitis C Virus (HCV)

A

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

20
Q

Immunopathology - Cytomegalovirus (CMV)

A

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.

21
Q

Immunopathology - Dengue Virus Infections

A

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.

  1. 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

22
Q

Dengue fever

A
  • malaise (discomfort)
  • high fever
  • headache
  • generalised arthralgia (pain in a joint)
  • myalgia (muscle pain)
23
Q

Severe dengue, which may include dengue shock syndrome (DSS), and hemorrhage.

A

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.

24
Q

problem with viruses and immunity?

A

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

25
Q

examples of non-enveloped viruses

A

Adenovirus
Norovirus

  • Repetitive Virus antigens
  • highly immunogenic
26
Q

Enveloped viruses;

A

derived from previous host cell membrane, will have some viral glycoproteins on the surface

Repetitive Virus antigens; highly immunogenic

The famous Heamagglutinin and Neuraminidase!

27
Q

CD8+ T cells are needed to attack infected cells

A

Acquired/adaptive Immunity
The humoral response = antibodies, produced by B-lymphocytes
effective at clearing cell-free viruses

The cellular response, mediated by T-lymphocytes
CD4+ T-cells (helper T cells)
CD8+ T-cells (cytotoxic T cells)
effective at clearing infected cells

28
Q

what are viral PAMPs and PRR’s

A

“foreign” nucleic acids, only exposed after virus entry

Virus-specific PRRs located inside the cell
Endosomal
Cytoplasmic