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Virology > Evolution of viruses > Flashcards

Evolution of viruses Flashcards

1
Q

What is the Baltimore classification?

A 
A way of grouping viruses based on genome nucleic acid differences
I - dsDNA
II - ssDNA
III - dsRNA
IV - positive ssRNA
V - negative ssRNA
VI - ssRNA w/ reverse transcription step
VII - dsDNA w/ reverse transcription step
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2
Q

What are some examples of dsDNA viruses?

A

Can have genomes from 5kb - 2.5Mb
Includes Herpesviridae, Poxviridae (cytoplasmic replication)
Adenoviridae (large) and papillomaviridae, polymaviridae (small)

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3
Q

What are some examples of ssDNA viruses?

A

Can have genomes from 2kb - 25kb. Replicate in the nucleus using host transcription machinery. Includes Parvoviridae.

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4
Q

What are some examples of dsRNA viruses?

A

Can have genomes 4 - 30kb. Includes Reoviridae (large) and Totiviridae (small). Have a core particle to hide genome from host immune system

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5
Q

What are some examples of + ssRNA viruses?

A

Can have genomes 2 - 32kb. Replicate in the cytoplasm, genome is the mRNA. Have an RdRp for genome replication and transcription. Includes Picornaviridae, Coronaviriae (SARS). Are diverse in eukaryotes.

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6
Q

What are some examples of - ssRNA viruses?

A

Can have genomes 11 - 25kb. Replicate in the cytoplasm (most), encode RdRp for replication and transcription which is packaged in the virion. Includes orthomyxoviridae (flu), rhabdoviridae, filoviridae.

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7
Q

What are some examples of retroviruses and pararetroviruses?

A

Can integrate into host genome and use host transcription and splicing machinery. Encode a reverse transcriptase. Includes Retroviridae and Hepadnaviridae.

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8
Q

Describe the types of plant viruses

A

Mostly + ssRNA. Do get some dsRNA and - ssRNA and pararetroviruses. Have found no retroviruses and no dsDNA viruses (apart from in algae).

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9
Q

How do plant viruses infect cells?

A

Have to get past the cell wall e.g. animal chewing on plant or an animal such as an aphid feeding. Virus needs to spread from cell to cell via plasmodesmata, so encode a movement protein. Virus can be transported as a whole or in parts.

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10
Q

Describe the types of bacteria viruses

A

Bacteriophages. Mostly dsDNA, a few ssDNA, very very few RNA viruses. They are very abundant and were used as an alternative to antibiotics in the Soviet Union. Are sprayed on meat in supermarkets. Host defence mechanisms include restriction enzymes and CRISPR/Cas9

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11
Q

Describe dsDNA bacteriophages

A

Main group is the Caudovirales which includes myoviridae, siphovirida and podovirida and tectiviridae (which is icosahedral)

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12
Q

How do dsDNA bacteriophages enter cells?

A

Recognise bacterial cell wall and inject the genome in under pressure through a protein needle. In gram negative bacteria, a lysozyme complex degrades the middle peptidoglycan.

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13
Q

Describe the types of viruses of Archaea

A

Not much known. Nearly all dsDNA, some ssDNA, no known RNA viruses. Many are not related to bacteriophages and have unusual morphologies e.g. pincers.

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14
Q

What are the giant viruses of amoebae?

A

Viruses with big genomes. Includes mimivirus which has a 1.2Mb dsDNA genome encoding 900 genes and a 0.6um particle; pandoravirus which has a 2.8Mb dsDNA genome encoding 2500 genes and a 1um particle. Have also found pithovirus from a permafrost sample which has a 0.6Mb dsDNA genome, 500 genes and a 1um particle. Size of these viruses overlap with small bacteria and some intracellular parasitic eukaryotes.

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15
Q

Describe virus-like entities

A

Have no capsid protein, is a selfish genetic element. Includes:
Satellite virus - encodes a capsid protein, needs a helper virus to replicate
Satellite nucleic acid - needs a helper virus for encapsidation and replication
Hepatitis delta virus
Viroids - circular ssRNA, doesn’t encode protein, in plants
Capsid-less viruses
Endogenous retroviruses and retrotransposons
Plasmids

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16
Q

Describe the hepatitis delta virus

A

Circular ssRNA, encodes 1 protein expressed in 2 forms by RNA editing. Needs HBV for envelope proteins and uses host RNA pol II for replication and transcription.

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17
Q

Describe some capsid less viruses

A

Mitoviruses (infect fungi mitochondria and are vertically transmitted)
Narnaviruses (infect fungi, transmitted vertically/during mating)

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18
Q

How do we know there is a common ancestry of RNA viruses?

A

All encode an RdRp, all of which have a common ancestor.

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19
Q

How can RNA virus phylogeny be determined?

A

Mostly by looking at the RdRp. In some deep branches have to use other features to resolve e.g. picorna-like helicase-VPg-protease-RdRp gene block. Get horizontal transfer sometimes - recombination with similar viruses/rare recombination with different viruses/acquisition of host genes means that virus evolution is a network rather than a tree.

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20
Q

What does evolutionary rate depend on?

A

What you are measuring. Could be mutations per site per replication, mutations between different cells in an individual, differences between individuals or differences between this years strain and last years strain.

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21
Q

What factors influence evolutionary rate?

A

Generation time, transmission (direct or vector), selection, genomic architecture, replication speed, viral enzymes (e.g. DNA repair), host enzymes, environmental effects

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22
Q

How can the evolution of viruses be studied beyond the previous few Myrs?

A

Short term substitution rates imply a common ancestor a few May. To push the timeline back, we can look at arctic samples of viruses (e.g. flu from 1918), look at introduction of yellow fever to the Americas and subsequent isolation (compare the american and african strains), look at plant viruses in permafrost

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23
Q

How can endogenous viral elements be used to study virus evolution?

A

Retroviruses integrate into the host genome (so do bornaviruses, hepadnaviruses sometimes, as well as RNA viruses if there is a co-infection encoding a reverse transcriptase and an integrase). Can be dated to before the last common ancestor if the integration is observable in many species - can work out when it occurred by comparing sequence similarity.

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24
Q

Describe the long term evolution of viruses

A

Whilst short term evolution is very fast (escaping immunity and adapting to new hosts), long term evolution is much slower due to restrictions by fundamentals. Viruses ‘cycle round in a box’ - viruses can evolve back to previous forms over generations of hosts (apart from if host antiviral evolution blocks this). Jumps in evolution are when viruses adapt to a new host (but not that different if its still a mammal, v different but v rare if not). Have found that major groups of viruses have existed in their current forms for 100s of millions of years.

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25
Q

What are the theories for the origins of viruses?

A 
Reduction hypothesis (from parasitic cells losing genome)
Cellular origin hypothesis (selfish genetic elements that escaped the cell)
Co-evolution hypothesis (evolved alongside ancestors of LUCA in the pre and post cellular RNA-protein world)
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26
Q

What is the evidence for the Reduction hypothesis?

A

Largely discredited, apart from regarding primitive pre-LUCA photo-cells as the DNA replication enzymes are unrelated

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27
Q

What is the evidence for the cellular origin hypothesis?

A

Plausible for small viruses (picorna-like viruses, retroviruses from retrotransposons, ssDNA viruses from plasmids) as they can be traced to cellular components. However the cellular elements may be derived from a pre-LUCA ‘virosphere’ in the RNA-protein world.

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28
Q

What is the evidence for the co-evolution hypothesis?

A

Plausible for large dsDNA viruses, and for the ancestors of RNA viruses

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29
Q

Describe the progression from the RNA world to the DNA world

A

RNA world: inorganic compartments form, selfish replicating ribozymes, potential protocells
RNA-Protein world: primitive ribosomes, evolution of genetic code, RNA viruses, protocells
RNA-DNA retro world: retroviruses and reverse transcription to stable DNA. Get DNA viruses and plasmids
DNA world: bacteria and archaea and eukaryotes develop.

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30
Q

How did viruses have a large role in evolution of cellular life?

A

Evolve quickly and can evolve novel proteins (even now).
Insertion into genomes of host - retrovirus elements in many genomes
Lateral gene transfer to hosts
Co-evolution of defence mechanisms for host and virus - drove immunity and programmed cell death, may have driven cell structure, organisation, DNA genomes, eukaryotic nucleus, antiviral mechanisms repurposed e.g. RNAi, DNA and protein modification, RNA processing
Likely to be the origin of introns

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31
Q

What is epidemiology?

A

The study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to the control of health problems.

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32
Q

What factors does epidemiology study?

A

Characteristics of people affected (e.g. factors that influence disease such as needle sharing)
Where cases occur
Time cases occur (short epidemic or long endemic)
Populations
Study of disease control

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33
Q

What are the levels of disease control

A

Control: reduction of transmission risks to predefined levels (e.g. bovine TB in UK)
Elimination: reduction of transmission risk to near zero (e.g. measles in USA - not present but someone could bring ini)
Eradication: reduction of transmission risk to zero (e.g. small pox)

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34
Q

Why is epidemiology important in disease description?

A

Knowledge of mode of transmission is important in understanding quarantine and containment. Need to know incubation period and period of communicability.

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35
Q

What is R0?

A

The reproduction number. Is a measure of the ability of an infection to spread throughout the population. How many cases a single case generates in a susceptible population

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36
Q

How does the value of R0 affect disease spread?

A

Needs to be bigger than 1 for infection to spread
An R0 of 1 indicates an endemic disease
The higher R0, the more difficult it is to control the disease and the younger the average age of infection.

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37
Q

What are some typical R0 values?

A

Measles is super high - 15-17
Polio is 5-6
Most (e.g. flu) are around 2

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38
Q

What determines R0?

A

Probability of transmission in a contact between infected and susceptible (can be reduced with barriers)
Frequency of contacts (depends on mode of transmission e.g. airborne/sexually transmitted) (can be reduced by staying home when ill, isolation, school closures)
Duration of infectiousness (use antiviral drugs e.g. HIV)

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39
Q

What is R?

A

R0 is for susceptible individuals only. R = R0 x proportion of susceptible individuals. Can be effected by immunisation programs and vaccines.

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40
Q

What is herd immunity?

A

Reduce risk of transmission through population by immunising some people - indirect protection.

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41
Q

how can herd immunity be calculated?

A

If R0 is higher, need a higher vaccine coverage - need 95% for measles.

42
Q

How can vaccine programs be designed for protection or herd immunity?

A

Measles is for protection (everyone gets it)
Flu vaccine is for herd protect - vaccinate school children as they are more likely to spread the virus through the population. Protect the elderly who are more at risk (but not a high uptake and immune senescence means it is less effective)

43
Q

What are the different types of epidemiology studies?

A

Descriptive (study amount and distribution of disease)
Analytical (study determinants and effects)
Randomised control trials

44
Q

Describe descriptive epidemiology studies

A

Amount and distribution of disease is investigated through case reports and case series. Also by comparing populations (not a strong design) and cross-sectional studies - collecting blood samples and looking for immunity/infection

45
Q

Describe analytical epidemiology studies

A

Study determinants and effects through observational studies and case control - compare case to control group. Track a cohort over time

46
Q

Describe randomised control trials

A

Best evidence from these. Communities are randomised and then tracked (e.g. for ebola vaccine - wanted communities to look at a cluster of people).

47
Q

What are the pitfalls of randomised control trials?

A

Conditions may be idealised - the effect of intervention may be over-estimated, and the scale up from a few people to a population may have more of a profound effect than the sample. For example, the Rotavirus vaccine wasn’t introduced due to cost until 2013 where there was a massive reduction in disease, bigger than expected from trials due to indirect effects.

48
Q

What do infectious disease epidemiologists try to analyse/predict?

A

Design and analyse studies
Disease surveillance
Estimating burden of disease
Outbreak investigation
Evaluate interventions (drugs/vaccine programs)
Molecular epidemiology
Mathematical modelling of disease transmission and control

49
Q

How do epidemiologists do disease surveillance?

A

E.g. GP practises report number of people with flu. Analyse if vaccine matches strain of flu found.
Need to work out how well your source tells you the information (e.g. not everyone goes to GP)
Study can allow plan for net flu season and check on the health service and monitor mortality.

50
Q

How do epidemiologists analyse burden of disease?

A

How well can surveillance pick up infection - e.g. not everyone goes to GP. Would need to do a cohort study
Depends on country - e.g. Rabies is not tracked in countries where it is still around. Can be estimated by size of dog population compared to humans, and prevalence of rabies and biting rate etc etc

51
Q

What is evidence synthesis?

A

Brining in evidence from a range of studies to one place

52
Q

How can outbreaks be investigated?

A 
Emergency planning
Have to detect outbreak first - are cases above the expected level?
Find cases - must be defined
Work out why it is spreading - interview cases, find common themes e.g. food
Test hypothesis (eat the food)
Find point of contamination or source
Control
Determine whether the outbreak is over
53
Q

What sorts of mathematical modelling are run?

A

Provides an approximation for real world, allows running of conceptual experiments. Depends on the number of susceptible people - has to be dynamic and include herd immunity effects

54
Q

What is the point of mathematical models?

A

E.g. in epidemics can analyse the effects of different strategies and test different options (as opposed to only 1 in real life) - can compare and analyse for cost-effectiveness. Was used to look at mumps susceptibility - variable vaccine uptake was fine in short term, in long term get outbreak at uni due to gaps.

55
Q

How do new infections emerge?

A

Through new behaviour, mobility, demography, technology, ecology, variability of viruses

56
Q

How can new behaviours lead to new infections?

A

Overcome of taboos e.g. sexual behaviour (such as HIV)

Drug abuse

57
Q

How can mobility lead to new infections?

A

Wars are associated with outbreaks

Air travel e.g. SARS in 2003

58
Q

How can demography lead to new infections?

A

Population growth can give dense cities for viruses to spread in

59
Q

How can technology lead to new infections?

A 
Medical (e.g. transfusion, transplantation - helped HIV spread - vaccination)
Food production (e.g. BSE crisis)
60
Q

How can ecology lead to new infections?

A

Contact with animals
Agriculture and fisheries - dense farming of animals in agriculture amplifies viruses which can spill into humans, deforestation results in movement of animals including insects, environmental pollution can lead to immune suppression as seen in marine animals, climate change give changes in flora fauna and insects.

61
Q

How did HIV emerge?

A

Moved from apes in 1920, was spread rapidly due to gay men and blood transfusions, epidemic wasn’t noticed until too late.

62
Q

What is the risk of stopping vaccination of eradicated diseases?

A

May make us more susceptible to related diseases such as cowpox and monkeypox (related to small pox). Are rodent diseases; monkey pox is closely related to variola and moved to prairie dogs.

63
Q

How has Dengue virus spread?

A

The Aedes Aegypti mosquito is the vector, and before 1970 was localised to specific places. Deforestation in 1970s along with building big cities and water reservoirs have allowed the insect to spread over south america, taking the virus with it.
Insect has been transmitted to the Netherlands through water in plants (bamboo) that contain midges and eggs - no virus has emerged yet.

64
Q

How has West Nile virus spread?

A

Presents as Encephalitis in only 1% of cases - most are asymptomatic, 20% get a fever. Is an insect borne virus that normally infects birds. If humans are fed on, they can also get sick. Outbreak began in New York, helicopters sprayed buildings to kill mosquitoes. Virus has spread, is slowly moving to Europe although there is competition for infection in our birds e.g. with Usutu virus. Many insect vectors can carry the virus

65
Q

How has Zika virus spread?

A

Is associated with microcephaly. Is an old virus (been aware since 1947). Moved from africa. Changes in ecosystems and distribution and development of new niches have allowed spread

66
Q

How did Ebola virus spread?

A

Took 3 weeks to identify the cause of the illness due to poor infrastructure and distrust because of unrest. In this time the virus had already spread. There were few hospitals due to war and economic breakdown, and the government was poor and not listened too. When the international response began, the outbreak was halted quickly by testing people for the virus and separating.

67
Q

How do respiratory viruses emerge in humans?

A

Large reservoirs of virus in hosts with lots of genetic diversity e.g. influenza A in birds, paramyxo (such as measles, mumps, nipah) and coronaviruses (SARS, MERS) in bats. Viruses don’t tend to jump from bats/birds to humans, tend to go into domestic animals first where there is more contact.

68
Q

How did SARS emerge?

A

Severe acute respiratory syndrome. Had a 10% fatality rate. Airports shut and lots of money was spent to prevent spread. Got to humans from bats to food eaten in china. virus spread quickly due to major cities in the US and across the world due to air traffic.

69
Q

How did MERS emerge?

A

Middle Eastern respiratory syndrome. Spread from bats to camels, is distantly related to SARS. High death rate, especially if obese.

70
Q

How did Hendra and Nipah viruses spread?

A

From bats to pigs and horses to humans. High death rate (might have just been in pigs and horses)

71
Q

What is a zoonosis?

A

When humans get a virus from an animal but don’t transmit it to other humans so R0 < 1 and there is no outbreak.

72
Q

How can the impact of emerging infections be reduced?

A

Track the spill over of viruses into domestic animals carefully - have extensive diagnostic and surveillance.
Novel vaccine and antiviral development strategies

73
Q

What are the complications of flu?

A

Pneumonia, ARDS - acute respiratory distress syndrome (if virus infects lower airways), secondary bacterial infections

74
Q

What are the different types of flu?

A

A, B and C. A and B cause seasonal epidemics. Are distinguished by their coat proteins. Flu A has many different types of HA and NA and many possible antigenic variation as found in birds.

75
Q

How many different HAs and NAs does Flu A have?

A

16 HAs

9 NAs

76
Q

What is significant about flu H5 and H7?

A

Evolve to become highly pathogenic avian influenza which infects poultry. Has 100% death rate. Is due to a cleavage site in HA - if basic residues accumulate at the cleavage site (as seen in H5 and H7), the protein can be cleaved by ubiquitous proteases that are found all over the body (such as furin) as opposed to being restricted to the respiratory system (such as trypsin like proteases).

77
Q

What is HPAI and LPAI?

A

Highly pathogenic avian influenza and low pathogenic avian influenza. HPAI arises in the H5 and H7 subtypes.

78
Q

Describe the H5N1 flu outbreak in 1997

A

Was HPAI. Poultry outbreak occurred in Hong Kong, all birds were killed to prevent outbreak. Also detected in China but was covered up. Virus spread, partly due to wild bird migration and infected chickens - couldn’t kill as primary source of protein. Lots of poultry died. Virus then transmitted to humans and could be lethal. Haven’t seen human to human transmission yet.

79
Q

Why is it that only H5 and H7 are associated with HPAI?

A

In the lab: a basic cleavage site inserted into H6 has shown to give systemic virus replication in chickens. Could be due to the RNA virus structure?

80
Q

What are the symptoms of H5N1 infection in humans?

A

Don’t see systemic replication. Same in monkeys. Found lots of damage to the lungs and damage to other organs (necrotic lesions) is secondary. Multi-organ dysfunction occurs due to severe lesions and virus replication in the lungs alone (ARDS). Virus displays extra respiratory spread but not systemic and high damage to alveolar epithelium

81
Q

How can the H5N1 flu virus affect neurological damage?

A

Not in humans but can occur in other mammals. Virus spreads from olfactory epithelium to olfactory bulb to the cerebrum to the cerebellum to the spinal cord. Is dependent on the basic cleavage site.

82
Q

How have we been able to study what makes flu transmissible?

A

Use ferrets as a model. Put 3 point mutations (as predicted from previous pandemics) in a virus and then infect a ferret. Pass to another ferret etc to drive natural selection. See what viruses end up being transmissible and what mutations they have - found 5 in total (the 3 original and 2 more)

83
Q

What mutations are required to make flu transmissible in mammals?

A

Changes to HA to increase avidity for attachment to receptor - includes some change to the receptor and loss of a glycosylation site
Fusion in the endosome often is impaired - need a mutation in PB2 to boost temperature stability (temperature of avian intestinal tract is 42; human airways is 33).
Useful to know as can now look out for these mutations and see if they are emerging or not

84
Q

Describe the H7N9 virus

A

Is an emerging virus which has many of the mutations associated with transmissibility. Still binds the avian receptor and has poor airborne transmissibility. Needs to develop pH and temperature stability mutations, but not many to go - needs to be watched in case of picking up mutations in chickens and then infecting an immunocompromised host in which natural selection can take place over a longer time.

85
Q

Describe the dynamics of a single strain outbreak

A

As outbreak continues, number of susceptible people decreases and therefore infections peaks and then declines.

86
Q

What is hard to know/predict about flu epidemics?

A

Time - could be december - april
Severity
Length of season
H3/H1/B virus
Where virus will be from (southern hemisphere, equator, asia, persist locally)
How similar it will be to previous strains.

87
Q

Describe the flu vaccine

A

Has 4 strains in the vaccine against the most common flus. Is the only vaccine that can be changed upon short notice, decision as to what strains to include in the vaccine are made 8 months before the flu season begins.

88
Q

When were flu vaccines first developed?

A

At the end of the second world war - worked at first but then stopped as the virus evolved. Vaccine was updated and worked for 2-3 years before the virus evolved again.

89
Q

What is antigenic cartography?

A

A piece of software that measures how similar each strain of flu is antigenically. Measures antigenic shift on 2 axis.

90
Q

How does the flu virus evolve to escape population immunity?

A

Jumps to a new antigenic cluster every ~3yrs as shown by antigenic cartography.

91
Q

How is flu analysed?

A

Strains are isolated from around the world and sent to 5 labs in which 20,000 viruses are sequenced for HA (and probs whole genome) and sent for analysis of evolution

92
Q

Describe evolution of the flu virus from 2002

A

In 2003, most viruses had a new antigenic structure, vaccine was updated. Was constant through winter in northern hemisphere.
In 2004, virus changed again
Vaccine updated in 2005, worked well for winter 2006
Virus evolved again in 2006
In 2007 and 2008 there was an issue with the assay so clusters looked weird
Virus evolved again in 2009
Between 2002-2006, virus evolved much more frequently that expected

93
Q

What was the problem seen in the HA assay for 2007 and 2008?

A

Virus had changed affinity for the turkey red blood cells used in the assay, leading to much larger clusters. When switched to guinea pig red blood cells all was fixed.

94
Q

What is the evidence suggesting that changes in the flu virus are driven by selection and not by random chance due to error prone replication?

A

When a human virus moved into pigs in the 1970s found that there was little antigenic evolution - that virus still circulates today. This is because there is fast turn over of pigs and naive pigs are constantly introduced. Shows that the virus doesn’t change antigenicaly unless it has to due to immune selection pressure - there is a cost.

95
Q

What is the minimum requirement for a flu virus to jump to a new antigenic cluster?

A

At least 4 amino acid substitutions in 2 antigenic sites - this will require a vaccine update. However, found that when mutating each individual residue only one of these moved the virus to a new cluster. In other cluster jumps found a double mutation was required. Also found that cluster jump could be reversed in the reverse mutation.

96
Q

What substitutions change the antigenic phenotype of the flu virus?

A

A mutation in/aroound site B (the receptor binding site). Need 1 substitution in 1 of 7 positions around the receptor binding pocket. Theorised to be because the receptor binding pocket itself must be conserved, but this is where most antibodies that matter (neutralising antibodies) bind (though antibodies bind all over globular head - an immune system decoy?). The cost of the change is the weakening of the receptor.

97
Q

How can we begin to design flu viruses to aid prediction of how the flu virus will jump to new clusters?

A

Have 7 possible positions for mutation and 20 amino acids - these mutants can be made in a lab and see which ones are replication viable. Then see which ones progress antigenic shift forward (don’t want to go back as will have immunity). Then look at receptor binding and if the mutation moves the virus to a new cluster. Can narrow down to 11 viruses, but only 4 move the virus to a brand new cluster. Then look at growth assay - found that the substitution taken in nature wasn’t the most likely (others grew better, but these were the revertants so wouldn’t be chosen OR required a completely different codon so mutation would be unlikely). Found that most mutations to jump from clusters only need 1 codon change (one needed 2)

98
Q

What are the caveats in the attempts to predict flu virus evolution?

A

Clusters were chosen that arose from a single amino acid transition
Virus was chosen that arose just before the cluster jumped (other mutations may have affected viability of receptor binding site mutation)

99
Q

How have we attempted to predict the direction of antigenic shift in the current H1 strain?

A

Random mutagenesis performed on the globular head of HA. Mix with human antisera and see which viruses were selected for and could grow. Found all mutations were in the same direction - now we must await the shift to see if it is right. Is odd that all viruses went in the same direction (was the same when performed with ferret sera). Suggests that antigenic direction is constrained.

100
Q

How does the immune system respond to flu vaccination?

A

Get new antibodies for the strain in the vaccine AND a big boost in levels of antibodies for previous infections - ‘original antigenic sin’/’back boost’.

101
Q

Could we vaccinate for the flu virus in the next cluster?

A

In a scenario in which the vaccine was updated just in time for the flu season - people with the new vaccine had the same amount of antibody in their serum as people vaccinated with the current strain. Suggests that we could vaccinate ahead and even if virus doesn’t jump to the next cluster there would still be protection, and that if you predicted the evolution wrong you would be no worse off. This is in clinical trials now.

Virology (13 decks)

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