Animal Viruses Flashcards
1
Q
What is a virus?
A
- they are obligate intracellular parasites that require a host cell to replicate
- they have an extracellular form called the virion which allows the virus to travel from one host cell to another
- they have absolute dependence on the host cell cannot replicate unlesss vririon has gained entrance into a suitable growing host cell - infection
- they are found everywhere and can infect all types of life
- most ubiquitous and diverse group of organisms on the planer, with a vast array not even yet been identified
- estimates suggest that they considerably exceed the total no of stars in the known universe; >10^23
2
Q
There are three main origin hypothesis
A
Progressive hypothesis
Regressive hypothesis
The virus first hypothesis
3
Q
The progressive hypothesis
A
also known as escalope hypothesis
Simple, mobile genetic elements that gradually evolved into more complex entities, became autonomous and could move between cells, like transposons
4
Q
The regressive hypothesis
A
also known as reduction hypothesis
Derived from a more complex progenitor - once independent in tracellular organism that may have shed non-essential components and regressed, unable to replicate independently
5
Q
The virus first hypothesis
A
also known as the ‘RNA world’
Viruses predate cells- exist as self-replicating units. This would make viruses the first form of life on earth
6
Q
Virus common structures
A
- structure:
Particles of genetic material, surrounded by a protein coat
Small size (100x to 1000x < average human cell)
Build de novo (from scratch) in each generation
Have no cellular components - Life:
Can’t perform metabolic processes
Do not grow
Don’t respond to environmental stimuli
Don’t reproduce (replicate)
Have no homeostasis - Qualities:
Cannot be cultured
Can evolve
7
Q
Viral components and activities
A
8
Q
Structure of a virus
A
- nucleic acid of a virion is surrounded by its
capsid - the capsid is composed of a number of individual protein molecules called capsomeres that are arranged in a precise and highly repetitive pattern around the nucleic acid
- the information required for the proper folding and assembly if viral proteins into capsomeres and then capsids is often embedded in the amino acid sequence of the viral proteins - when this is the case the virion goes through self - assembly
some virus protein and structures require assistance from host cell folding protein and assembly - they can be naked as described before or enveloped
- Enveloped have a lipoprotein membrane surrounding the nucleocapsid
- envelope if present assists in infection by fusing with the host membrane
- They also exit more easily from animal cells
9
Q
Virus symmetry
A
- rod shaped viruses have helical symmetry (starched disc with helical centre)
- Length of these is determined by the length of the nucleic acid
- spherical viruses have icosahedral symmetry (most common)
- Width is determined by size and packaging of the capsomeres
few viruses have a complex architecture that is not strictly helical or icosahedral e.g smallpox
10
Q
Retroviral replication
A
- Reverse transcriptase synthesises a ssDNA from ss(+)RNA
- RNA template is degraded
- dsDNA is synthesised = proviral DNA
- Integrase recognises and binds provirus LTRs
- Provirus + integrase enters host nucleus
- Integrase cuts host genome randomly
- Integrase inserts provirus into host genome
- 5’ LTR acts as a promoter, driving viral gene transcription using host’s machinery
11
Q
Life cycle overview
A
- Attachment (adsorption) of the virion to the host cell
- Penetration (entry, injection) of the virion nucleic acid into the host cell
- Synthesis of virus nucleic acid and protein by host cell machinery as redirected by the virus
- Assembly of capsids and packaging of viral genomes into new virions
- Release of new virions from the cell
- virion - complete, fully developed infectious viral particle
- Host cells supporting virion replication are called permissive
- uncoating - loss of many or all of the virus proteins, either while attaching to the host membrane, or upon insertion
12
Q
One step growth curve parts
A
Eclipse
Maturation
Latent period
Release
13
Q
Eclipse
A
- Eclipse - (first few minutes after injection) genome is replicated and the proteins are synthesised
- Once attached to a permissive host cell a virion is no longer available to infect another cell
- This is followed by the entry of viral nucleic acid into the host cell
- If the infected cells break open at this point the virion no longer exists as an infectious entity since the viral genome is no longer inside its capsid
14
Q
Maturation
A
- Maturation - (begins as newly synthesised viral nucleic acid molecules become packaged inside their capsids) - number of infectious virions inside host cells rise dramatically
- However new virions still cannot be detected in the culture medium unless cells are artificially lysed to release them
15
Q
Latent period
A
Happens as newly assembled virions are not yet presented outside the cell
16
Q
Release
A
at end of maturation mature virions are released either by lysis or by budding or excretion depending on the virus
- Burst size - the number of virions released per cell - this varies with the particular virus and the particular host cell and can range from a few to a few thousand
- duration of replication cycle also varies
17
Q
Types of viral infections
A
Non permissive
Permissive
18
Q
Non permissive infection
A
Virus not allowed entry
19
Q
Permissive infection
A
Virus enters the cell
20
Q
Types of permissive infections
A
Acute or lysis
Persistent or chronic
Host survives
Latent
Transformation
Abortive
21
Q
Acute or lysis
A
Virus replicates, progeny released, cell dies
22
Q
Persistent of chronic
A
Virus replicates, progeny released, eventually infection is cleared, host survives
23
Q
Latent
A
Virus present in cell for life and may replicate
24
Q
Transformation
A
Virus causes cell immortalisation
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Abortive
Virus enters the cell but fails to replicate
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Chain of infection
A) a pathogenic agent
B) a susceptible host
C) environment
- chain : spread of an infection within a community
- composed of several interconnected steps
- Agent leaves its host through a portal of exit and enters another susceptible host through portal of entry
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Disease reservoirs
- A population in which an infectious agent remains viable (habitat) for long
- May or may not be able to transmit infection
- May or may not show clinical symptoms
- e.g bats
28
Disease carriers
- Hosts with no apparent clinical symptoms, able to transmit infection such as:
- Asymptomatic
- Subclinical
- Incubatory
- Convalescent
- Chronic
- e.g Typhoid Mary
29
Convolution and coadaptation of virus and host
Viruses are not fixed - unchanging entities; they are subject to evolutionary pressures and undergo constant evolutionary changes
30
Examples of coevolution and coadaptation
- myxoma virus intentionally introduced to control wild rabbit population in Australia and Europe. Mortality rate among infected rabbits is high, ~99%
- First year; >95% of rabbit deaths
- after six years: rabbit deaths dropped to ~30%
- overall:
- Virulence decreased by ~80% and maintained
- outcome:
- Rabbit population evolved to reach equilibrium with pathogen
31
Viral evolution - antigenic drift
- Mutations to original virus that lead to a new strain
- new strain can be closely related to progenitor
- if host recognises the new strain it responds (“cross protection”)
- If not, host can be infected with new strain (~25% success of flu vaccines)
- examples; Flu (common cold), Influenza A and B
32
Viral evolution - antigenic shift
- different viruses infect a host, combine and reassort their genome
- abrupt, immediate and substantial change
- Able to cross species barrier
- absent population immunity; pandemic
- e.g. COVID-19, Influenza
33
Pathogenic stages of a “typical” viral infection
1. Host entry - virus invades an colonises the host
2. Incubation - time between infection and onset of symptoms
4. Illness with symptoms
5. Decline of infection - systems subside
5. Convalescence - patient regains strength and returns to normal
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Modes of transmission
Direct and indirect
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Direct mode of transmission
Infected host transmits pathogen directly to a susceptible host without an intermediary
36
Indirect mode of transmission
- occurs when transmission is facilitated by a living or non living intermediary
- common vehicles:
- food (e.g. Preparation)
- fluids (e.g. Blood, water)
- air (e.g. Airborne droplets)
- Living vectors (e.g animal bites)
- contaminated objects - surfaces
- zoonotic transmission (e.g. Animal contact, food chain)
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Basic reproduction number
R0
38
R0 < 1
Infection will decline and eventually disappear
39
R0=1
Infection remains steady
40
R0 > 1
Infection will spread exponentially
Example:
- 100 students
- viruses with different R0
- student interact and spread the virus based on their R0
41
Geographic scope of viral disease - based on R0
Endemic
Epidemic
Pandemic
42
Endemic
Constantly present at low numbers in a geographic area. Population is considered a reservoir
43
Epidemic
Occurrence in unusually high numbers in a geographic area. Population is considered carriers
Check notes for graph
44
Pandemic
A global epidemic - with time will become endemic
45
Emerging and reemerging of infectious diseases
Disease emergence results from complex and multifactorial interactions between pathogens and hosts
emergent
Re- emerging
Pathogen adaptation can contribute to disease emergence
46
Emergent
Disease that suddenly become prevalent
47
Re-emerging
Diseases under control that become prevalent again
48
Disease incidence and prevalence
Both relate to disease frequency, but present different aspects of disease occurrence
49
Disease incidence
Number of new cases in a population, in a given time period
A risk indicator
50
Disease prevalence
Total number of existing and new cases in a population, at a given point in time
A “snapshot”
51
Morbidity, mortality and fatality rate
Means of ranking infection severity and tracking disease trend
52
Morbidity
Infection incidence within a given population
53
Mortality
Death incidence within a given population
54
Fatality rate
Percentage of infected who die from infection
55
Extent of transmission
In depend on several parameters
56
Factors affecting relative disease incidence
- Geographic location of carriers/reservoirs
- Climate (humidity, UV radiation)
- Circadian clock
- Virus and host migration patterns
- socio-economic conditions (nutrition, sanitation, clean water
- genetic profiling (MHC)
- Age at infection
57
Factors affecting disease severity
- cell type tropism
- viral load
- type of host entry
- host immune system relationship
as a pandemic continues, natural selection is expected to increase the frequency of alleles that favour survival
58
Disease surveillance and public health
Check notes
59
Active immunity
co-ordinated action of white blood cells, protein, and receptors that sense the presence of a virus, control infection, and provide long term immunity or resistance against it
60
Intrinsic response/cellular
- constantly present
- immediate response
- tends to be antigen specific
- blocks/limits infection
- multi factorial - autophagy, altos is, chemical barriers, RNAi
- isolates diseased cells
61
Innate response/systemic
- First line of defence
- immediate response
- antigen independent
- short lived
- multifactorial - NK - cells, phagocyte
- prevents disease spread
62
Adaptive response/systemic
- second line of defence
- takes days to weeks to develop
- antigen specific
- long lasting
- tailor made - T/B clonal expansion
- fights infection - prevents re-emergence
63
Response cells
the innate and adaptive immune responses are mediated by several types of leukocytes that stem from hematopoietic stem cell precursors and mature through either the myeloid or the lymphoid lineage
64
Vaccination
Vaccination: intentional inoculation with a harmless viral form to induce immunological memory the same way a primary infection would do
65
Smallpox vaccination
30% mortality rate
16th century, China: pulverised dried smallpox scabs inhaled or injected into uninfected persons
17th century England: cowpox human lesions, used to vaccinate healthy humans against small pox
66
Features of a live attenuated vaccine
A weakened virus
67
Advantages of a live attenuated vaccine
Strong response
Long lasting immunity
No need for booster vaccine
Cost effective
Look at notes
68
Disadvantages of a live attenuated vaccine
Needs refrigeration,
May revert to pathogenic form
69
Examples of a live attenuated vaccine
MMR, chickenpox
70
Features of an inactivated vaccine
Dead virus extract
71
Advantages of an inactivated vaccine
Stable
Mass produced
Easy to transport
Cost effective
72
Disadvantages of an inactivated vaccine
Need booster
May not be sufficiently immunogenic
73
Examples of an inactivated vaccine
Polio, influenza
74
Features of subunits - VLPs
Based on recombinant technology, delivers part of virus
75
Advantages of subunits - VLPs
Safest
Good immune response,
Good solution for viruses that don’t replicate well in cell culture
76
Disadvantages of subunits - VLPs
Lower immunogenicity
More expensive
Difficult to produce
Need booster and/or adjuvant
77
Examples of subunits - VLPs
HPV, HBV, Covid-19
78
Features of virus vector
Antigen expressed by and delivered via an attenuated viral vector
79
Advantages of virus vector
Good immune response good solution for viruses that don’t replicate well in cell culture
80
Disadvantages of virus vector
Need booster
May revert to pathogenic form
Can cause a reaction
81
Examples of virus vector
Ebola, Covid-19
82
Features of mRNA vaccine
Instructs cell how to produce the antigen
83
Advantages of mRNA vaccine
Quick production
Stable
Safe
Cost effective
Easily modifiable
84
Disadvantages of mRNA vaccine
Needs freezer storage
Need for booster
85
Examples of mRNA vaccine
Covid-19
86
Passive immunity
- transfer of antibodies from one individual to another, or manufactured
- offers immediate but temporary protection
- there are 2 main types
1. Natural; maternal antibodies (in utero through the placenta, and after birth during breastfeeding) - early protection for newborns which fades within months
2. Artificial; serum antibodies (immunoglobulin treatment) - immediate immunity but NOT long term memory
87
Infection control - antiviral drugs
- challenges:
- Distinguish between virus and host
- minimise building up of drug resistance
- can have side effects
88
Inhibition of host entry
Using fusion inhibitors
89
Inhibition of viral uncoating
Amine inhibitors
90
Inhibition of retroviral genome integration
Inter grase inhibitors
91
Inhibition of genome replication
Nucleoside analogues
92
Inhibition of particle release
Neuroamidase inhibitors
93
Herd immunity and infection transmission
- definition: resistance of a group to an infection, due to immunity present in a large proportion of the group members
- means: natural infection, vaccination, natural immunity
- outcome: break the chain of transmission, protect vulnerable members of a population
- threshold; the level of immune people required to achieve herd immunity depends on disease infectiousness, represented by the basic reproduction number, dynamic relationship with the environment
94
Measles and herd immunity
- first licenced in 1963
- intensive vaccination programme initiated in 1968
- her immunity (through natural infection, or vaccination) continuously protects the general population
- re-emerging outbreaks are dealt with swiftly
- lifelong immunity
