Viral properties and disease Flashcards
Define the nature of viruses, and summarise a generic life cycle of a virus, explaining its parasitic nature in relation to the host cell Explain the basis for the classification of viruses, and how viruses are detected, cultivated and manipulated Viral routes of infection: explain the different routes by which viruses cause infection, define the term tropism, and explain what determines the tropism of a virus Viral infection outcomes: list different outcomes of infection by viruses, acute in
What is the generic size of viruses?
Very small. 100nm. Can only be seen by electron microscopy.
How can it be proven that a virus causes a disease according to Koch’s Postulates? (x2)
Microorganism found in large numbers in all diseased animals, but not in healthy. The organism must be isolated, grown, purified and injected into healthy animals. Those healthy animals must produce the same disease, and those suspected microorganisms recovered and compared to the first microorganism as the same that was isolated. NOT ETHICAL.
What are viruses? How is genetic material contained?
Obligate (intracellular) parasites. DNA OR RNA.
How do viruses briefly work inside cells?
Viral genome replicated and directs synthesis of more viral components and genomes by manipulation of cellular systems.
What are the three virus morphology types?
Non-enveloped: have symmetrical protein CAPSID (protein shell of virus).
Enveloped: lipid envelope derived from host cell membrane of the last cell it replicated (virus leaves previous host cell and buds off using the cell’s membrane).
Some are a combination of both (capsid around genome and envelope around that).
How are viruses classified? What is the classification called?
How they carry their genes (DNA, RNA) and the mechanism of transcription. Baltimore classification.
Give three examples of different viral classes. (This is just for broader understanding).
DNA genome –> RNA –> Protein
Negative sense RNA –> DNA –> RNA –> protein (photo attached)
(Positive-sense m)RNA –> Protein
7 classes describing genetic material and transcription mechanism – some more complicated.
What are the consequences of virus having an RNA genome? (x2(x1)).
Have to use their own polymerases to replicate because body doesn’t replicate RNA. These lack proof-reading mechanisms leading to higher mutation rate. RNA genomes small because of instability. So tend to be simpler.
What are the consequences of virus having DNA genome? (x2(x1)).
Hold a lot of information. So, lots of room for accessory genes which can modify the host immune response. Can impose more difficult packaging strategies.
What is the generic life cycle of viruses? (x6 stages).
1) Find cell. Protein shell of virus binds to viral receptors on cell. But they are not actually virus-specific receptors – they are normal receptors for normal cell function which are exploited by viruses. 2) Virus uncoats (removes envelope/capsid) so genome has access to cell machinery. 3) (Synthesise mRNA) and exploit ribosomes in cell. 4) Proteins synthesised. Early-proteins: turn cell into into virus factory, OR late-proteins: form capsid or coat (protein components of virus). 5) Replicates genome by using its own or the cell’s polymerases. 6) Newly synthesised proteins and newly synthesised genomes join to create viruses which bud out of cell and spread.
How are viruses studied in the laboratory?
Too small, so study viruses by looking at effect on cell. Light microscope.
What do viruses do to appearance of cells in a tissue? What is this effect called? How can live/dead cells be distinguished?
Cells infected with virus: cells become round, dense, and then clump together. Called cytopathic effect (diseased state). Live cells will pick up stain, and dead cells (from cytopathic cell) don’t pick up stain.
What two mechanisms cause the cytopathic effect of viruses?
Cytopathic effect is the result of: mechanism of virus taking over the cell machinery; cells shut themselves down to save organism.
What do viruses leave to tissues?
Plaques – holes in the cell layer where virus has infected a cell and viruses have burst out and effected surrounding cells.
What do plaques tell us about our sample? How are the number of plaques determined in the laboratory?
Counting plaques tells us how many viruses were present in the sample that we put on the tissue in the first place. Titrate sample (e.g. urine) and make a series of 10-fold dilutions. Count plaques and extrapolate dilution back to determine amount of virus in clinical sample.
What is the alternative to plaques?
Some viruses may fuse cells together instead – forming a SYNCYTIA. Counting number of syncytium tells us number of viruses.
How can you determine where the virus is in a sample?
IMMUNOSTAINING. Generate antibodies that are unique to the virus proteins, add a fluorescent dye. You can use this to determine which cells are infected with the virus and what parts of the cell the virus proteins are located.
What is the nature of viral population growth?
ECLIPSE PHASE – start, where virus decreases in population – time where the virus goes INTO the cells and manipulates cell machinery.
Log growth curve.
Exponential because each infected cell = many more viruses synthesised.
Plateaus when all cells in petri dish used up and killed by virus.
How is a viral diagnosis done when i)we know what virus we are looking for (x2); ii)when virus is new (x2); iii)studying prevalence after infection?
i)Virus sample from patient in question is taken. Viral genome is extracted from sample and primers specific to part of the genome we are looking for mixed. If virus we are looking for is present, it will be amplified to a level we can detect. Sometimes, may use procedure that detects proteins and antigens of the virus (IFA (immune-fluorescence antibodies like explained in the immunostaining question), ELISA). ii)use electron microscopy (difficult, expensive, not sensitive). OR hemagglutination assay. iii)Diagnose after infection by taking blood of somebody who you think may have had that virus. Perform serology and look at antibodies in population. May help to determine if widespread vaccination needed.
What is needed for cultivation of virus?
Permissive cells and the environment needed for those cells to live. NB: Some viruses cannot be cultivated because they require more than just the host cell.
How are viruses manipulated in the lab?
Viruses are small so, we can make a virus from scratch. If we know the sequence of a virus genome, we can make that virus, introduce ONLY the genome into the cell (because when virus enters, it uncoats anyway), and many more viruses will grow (including the protein components). This is called reverse genetics – allows us to make viruses at will with mutations engineered into their genomes. This means that we don’t have to do long-winded attenuation in a different cell to evolve it into a vaccine.
What are the routes of transmission of viruses? (x8) RODZ By SMG
Respiratory (droplets), Faecal-oral (contaminated water), direct contact (saliva, fomites (contaminated surfaces)), Zoonoses (caught by animals and insect bites), blood (sex, transfusions), sexual contact, maternal-neonatal, germ line (can never get rid of them). RODZ By SMG
What does iatrogenic mean?
Transmission by healthcare worker.
What does Nosocomial mean?
Transmission type where infection caught in hospital.
What does germ-line transmission mean?
Part of the host genome (eg. Integrated retrovirus). And a type of vertical transmission.
What are viruses called when they are passed by insects?
Arboviruses.
What are the types of dissemination in virology? (x4) How can each be categorised on the basis of their interaction with epithelium? (x2)
Dissemination – means spread (from site of entry). Local infection (infection localised and does not spread) Primary viraemia (spread in blood) Amplification (replication in another organ) Secondary viraemia (spread AGAIN in the blood to ANOTHER organ). All epithelia are polarised. Outer side is apical side. Inner side is basal side (in contact with blood). Local – infection goes in and out by apical surface. Dissemination – infection goes in apical and out via basal surface.
What is a systemic infection? How is it symptomatically characterised?
Throughout whole body. Systemic infection often indicated by viral rashes. Virus leaves blood. Goes to skin. At this stage, host is contagious and virus looking to transmit to new host.
What is a haematogenous infection?
Found in blood.
What is a tropism of a virus?
Particular place a virus is replicating. Therefore defined as the preference of a virus to infection certain tissues and not others.
What is tropism of a virus determined by? (x3)
SUSCEPTIBILITY – whether the viral coat can latch onto a particular cell by receptor interaction. PERMISSIVITY – can virus complete replication in host cell. Whether virus is compatible with the genes expressed in that type of cell. ACCESSIBILITY – whether virus can reach a tissue.
What is pathogenicity?
Ability of the virus to cause disease.
What is virulence?
Capacity of a virus to cause disease depending on amount of replication and dealing with the host response.
What are the different outcomes of viral infection? AAPO
Acute infection (followed by viral clearance) Acute infection (but followed by accidental damage which can be permanent despite viral clearance – not part of virus’ strategy for replication.) Persistent infection
· Latent (do not replicate, but they are in your cells and can reactivate at any time).
· Slow infection.
Oncogenesis
AAPO (from the Simpsons)
What is the mechanism of acute infection?
Couple of days. Virus established infection and population growth. T and B-cells recruited to site of infection and virus CLEARS (viral clearance).
Examples? (x5 (x1 accidental pathogenesis)). Why do such viruses continue to circulate in population even if everyone in population has had it?
Influenza Smallpox (so virulent –> most often leads to death) Dengue fever. Rubella Poliovirus (has accidental pathogenesis – e.g. causes paralysis by reaching motor neurones) Continue to circulate in population by antigenic variation. So, immunity in population can mean little.
What is the mechanism of latent-reactivating, persistent infection?
Virus there, but not producing any proteins so immune system cannot detect it.
Reactivation occurs when immune system is a bit lower and so does not control the virus population as it would.
Latent infection examples? (x1)
Herpes SIMPLEX virus.
What is the mechanism of slow, persistent infection?
Long incubation periods.
Can suddenly flare up one day and die.
Slow infection examples? (x2)
Measles SSPE. HIV.
Strategies viruses can persist? (x2)
· Evade immune surveillance by manipulating immune system.
· Infecting tissues with reduced immune surveillance e.g. skin and immune-privileged nervous system.
What is the mechanism of oncogenesis from virus?
Some viruses that last a long time in the body cause cancer. Encode oncogenes which interfere with the cell cycle.
Oncogenesis infection examples? (x4)
Human Papillomavirus. Other Herpes viruses. Hepatitis B and C.
What affects outcome of virus infection?
Virus sequence (type of virus)
Virus load (how much you have inside you/took in) e.g. first child to contract chicken pox often has milder illness that the second child because second child is in closer contact and so infected with higher dose.
Host immune response/status (who you are? What diseases have you been exposed to recently?)
Host co-morbidity (what else have you got going on e.g. have you got asthma? In which case, you would fare less well with a respiratory virus).
Coinfections (any other infections at the moment).
Other medications
Host genetics
Age
Gender
What are emerging and re-emerging viruses?
An emerging disease is defined as a new infection resulting from the evolution of an existing pathogen, resulting in a change of host range (infection crosses species barrier and can finally infect humans), change of vector, pathogenicity or strain; or the occurrence of a previously unrecognised infection or disease.
A re-emerging disease is considered an already known disease that either shifts its geographical setting or expands its host range, or significantly increases its prevalence.
MOST ARE CAUSED BY ZOONOSIS (animals and arboviruses).
What is host range?
The range of host species or cell types which a particular virus, bacteria, or parasite is able to infect.
What is a quasispecies in virology?
In a virus population, there is genetic variety between individual viral genomes because of mutation accumulation (viruses have high mutation rate). A quasispecies describes this population in a SINGLE HOST.
Why is there genetic variety in a quasispecies?
Polymerase makes lots of errors in the virus.
What is a quasispecies shaped by? Give two examples?
The quasispecies will be shaped by repeated bottlenecks.
One crucial bottleneck is point of transmission where often, only one virus (with one version of the genome) will seed the host. So at the beginning of infection, quasispecies will not be very diverse.
If conditions change in a body e.g. drug administered, make-up of quasispecies will also change, and ones with beneficial mutations will outcompete other viruses.
What are the ways that of viruses can emerge? (x2)
Zoonosis – from animals.
Genetic variation e.g. antigenic drift [look at ‘Viral Properties’ deck].
Increased animal contact/overcrowding.
How can viruses re-emerge? (x1(x3))
Increased exposure through:
Though increased travel
Spread of vectors (e.g. mosquitos from global warming).
Immunosuppression.
MANY MORE…
Emerging diseases – examples? (x6)
HIV – from primates
Ebola – from bats
SARS – from bats. Cats were an intermediate animal.
MERS (Middle East respiratory syndrome) – from bats and camels.
Influenza – some kinds have emerged by antigenic shift from reassortment e.g. people are currently concerned about Avian influenza H5N1: present in high number of birds. People scared that in the future, the mutation will mean humans become infected and host range expanded.
Zika – New Zika strain evolved and caused the outbreak seen in the news. Mosquitoes
