Pathophysiology of viral infection Flashcards

(39 cards)

1
Q

What is the Ro

A
  • how many new infections one person will generate during their infectious period
  • approximate
  • vary by outbreak, mode of transmission and location
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2
Q

Give an example of a virus that harms a particular group of the population

Describe it

A

ZIKA Virus

  • it causes birth defects (microcephaly) in babies born to some infected mothers
  • microcephaly is underdeveloped heads and brain damage
  • its also associated to guillain-barre syndrome: the immune system attacks the nerves
  • transmitted via mosquitoes
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3
Q

What is a virus?

+ structure, size, MOA

A
  • particle containing nucleic acid and a protein coat +/- envelope
  • small in size (100x smaller than somatic cells, 10-400nm)
  • obligate intracellular- only replicate inside living cells
  • can infect range of organisms: humans, animals, plants, bacteria
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4
Q

How can the nucleic acid in viruses be described?

A
  • DNA or RNA
  • ds or ss
  • +ve/-ve/ambisense
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5
Q

What is a nucleocapsid?

A

= nucleic acid + protein coat

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6
Q

What is a virion?

A

= complete intact virus particle (the physical particle in the extracellular phase which is able to spread to new host cells)

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7
Q

Briefly outline the tasks a virus must do in order to grow

A
  • identify which cells to enter and how
  • know how to replicate inside the host cell
  • know how to exit and move between host cells as well as to a new host to persist in nature
  • develop mechanisms to evade host defences
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8
Q

Outline the stages involved in pathogenesis

A
  1. encounter: virus meets host
  2. entry: virus enters host
  3. multiplication: virus replicates in host
  4. spread: virus spreads from site of entry
  5. damage: due to the virus itself, the host response or both
  6. outcome: host or virus wins, or coexist
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9
Q

How can viruses enter the body through the skin?

A
  • abrasions
  • insect/animal bites
  • needle punctures
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10
Q

Gastroenteritis viruses enter via alimentary tract

What makes this tract a hostile environment?

A
  • extreme acidity/alkalinity

- digestive enzymes

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11
Q

What makes the urogenital tract a hostile environment?

How can viruses enter?

Give an example of a urogenital tract virus which causes local infection, and one which causes systemic infection

A

Low pH

  • via mucous membranes
  • abrasions

Local- HPV
Systemic- HIV

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12
Q

How might localise infection of the eye present?

And viral spread?

A
  • conjunctivitis

- Eye blindness/CNS

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13
Q

Describe the baltimore system for viral classification

A
  • By knowing the nature of a viral genome we can understand the steps it must take to produce mRNA needed to make viral proteins
  • identifies 7 pathways to creating mRNA

https://www.virology.ws/2009/08/12/simplifying-virus-classification-the-baltimore-system/

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14
Q

What happens after a virus replicates at the site of infection?

A
  • Some remain localised within epithelium/within one system

- some cause disseminated infection: inflammation compromises integrity of cell basement membrane

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15
Q

What does apical viral release and basolateral release mean?

Give examples

A

Apical

  • facilitate viral dispersal but not into underlying tissues
  • e.g. flu

Basolateral

  • provides access to underlying tissues and can facilitate systemic spread
  • e.g. rabies
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16
Q

Give 4 methods viruses can enter blood

What does this mean for spread?

A
  • Directly through capillaries
  • By replicating in endothelial cells
  • Through vector bite
  • By lymphatic capillaries

Virus now has access to most tissues

17
Q

What is primary/secondary viraemia?

A

Primary viraemia: This is when the virus enters the bloodstream (from inital site of infection).
Secondary viraemia: This is when viraemia has caused an infection in another organ or tissue by spreading through the bloodstream.

18
Q

What is passive/active viraemia?

A
  • Passive: viral entry into blood without active viral replication as in mosquito inoculation
  • Active: viral entry into blood following replication in site of infection and release via basolateral membrane e.g. measles
19
Q

How can viraemia be of diagnostic value?

How can it be a practical problem?

A
  • Used to measure viral replication/density

- Means we need to screen blood donors

20
Q

Describe neural spread of viruses

A
  • less common than haematogenous spread

- can go from periphery to CNS or vice versa

21
Q

Consider neural spread of viruses

What do the following terms mean?

a. Neurotropic
b. Neuroinvasive
c. Neurovirulent

A

a. virus can infect neural cells
b. virus can enter CNS from peripheral sites
c. virus can cause disease of nervous tissue

22
Q

Describe the following viruses in terms of neuroinvasiveness and neurovirulence

a. HSV
b. Mumps
c. Rabies

A

a. Neuroinvasiveness: +
Neurovirulent: ++++

b. Neuroinvasiveness: ++++
Neurovirulent: +

c. Neuroinvasiveness: ++++
Neurovirulent: ++++

23
Q

What is tissue tropism?

A
  • the cells/ tissues which support growth of a pathogen

- can be limited or pantropic

24
Q

What are the determinants of tropism?

A
  • Cell receptors: e.g. HIV required CD4+
  • Cellular proteins that regulate viral transcription e.g. John Cunningham (JC) virus requires viral enhacers in oligodendrocytes
  • Cell proteases e.g. flu requires serine protease
25
Viral genes are what causes them to be virulent. How so?
Genes that - affect ability of virus to replicate - modify hosts defence mechanisms e.g. virokines and viroceptors - enable spread of virus - have intrinsic cell killing effects
26
How do cytolytic viruses injure cells?
- inhibition of host proteins and RNA synthesis- leads to loss of membrane integrity - syncytium formation (multinucleated giant cells) - induction of apoptosis
27
How do non-cytolytic viruses injure cells?
Immune mediated - CD8+ mediated - CD4+ mediated - B cell mediated
28
How else can viruses injure cells?
- cell injury associated with free radicals
29
Give an example of a virus transmitted via the following routes: a) skin/mucous membrane b) respiratory tract c) faecal oral d) blood borne e) sexual transmission f) vertical transmission
a) Herpes (HSV-1,2), Chickenpox (VZV b) influenza, coronavirus c) Hep A (HAV), norovirus d) HIV, Hep B (HBV), Hep C (HCV) e) HIV, HSV-1,2 f`) HIV, CMV
30
When can vertical transmission take place?
- Antenatal: transplacentally - Perinatal - Postnatal: breast milk
31
What underpins chronic/persistent viral infection Give an example of a virus that causes it
- Continuous replication - Latency: times when restricted viral gene expression Lymphocytic choriomeningitis virus,
32
Consider latent infection Which kind of viruses cause it? Why does it happen? Presentation
- DNA viruses or retroviruses - Persistence of viral DNA due to a) extra chromosomal element as in HSV b) integration in host genome as in retroviruses - This causes viral genome to be replicated along with host cell chromosomes during cell growth HSV reactivation: fever, blisters, cold sores Retroviruses can result in transformation of the cell --> cancer
33
Describe the relationship between virus growth and adaptive immune response in acute infection
- A threshold level of virus must be reached in order to activate the adaptive immune response - During the induction of this response, virus growth continues to increase - Once adaptive response is achieved , growth declines until the virus is cleared - Memory begins once virus is cleared
34
How is chronic infection different to acute infection?
- The acute infection is a non equilibrium process: host response and virus infection change continually until resolution - Equilibrium is reached in chronic infection
35
Describe how viruses evade immune system with examples
Antigenic variation- flu, HIV, Rhinovirus Inhibition of antigenic procession - blocking transporter associated with antigen processing: HSV - removal of MHC-1 molecules from ER: CMV Production of cytokine receptor homologues - IL-1, IFNy: Pox viruses, Vaccinia - Chemokine: CMV Production of immunosuppressive cytokine - IL10: EBV Infection of immunocompetent cells: HIV
36
Describe the structure of Influenza A
- Contains segmented -ve RNA genome - Surrounded by matrix protein - Expresses neuraminidase (NA) and hemagglutinin (HA) - M2 ion channel protein on surface too
37
How does influenza evade host defence mechanisms?
- Antigenic variation: the immune system no longer recognises surface antigens as they change - Mechanisms of AV are antigenic drift and antigenic shift
38
What is antigenic drift?
- generates minor change in virus | - point mutations lead to changes in amino acids in two surface proteins HA and NA
39
What is antigenic shift?
- generates new influenza A subtypes which emerge at irregular intervals giving rise to pandemics - new strain is highly pathogenic MOA 1. Genetic reassortment of RNA: requires coinfection of a host with avian virus 2. Trans-species transmission of an avian influenza virus to humans. Adaption to growth in new host occurs as a result of spontaneous mutations --> emergence of pandemic strain