The Viruses Flashcards
What is a virus?
An infectious, often pathogenic agent or biological entity which is typically smaller than a bacterium, which is able to function only within the living cells of a host animal, plant, or microorganism, and which consultants of a nucleic acid molecules surrounded by a protein cost, often with an outer lipid membrane
Viruses are metabolically
Inert
What do viruses rely on their host cells for?
- energy
- metabolic intermediates
- protein synthesis
- replication environment (obligate intracellular parasites)
What are the enzymes in a virus mostly geared towards?
Infection
Virion
- An extracellular virus particle than can move from one cell to another
- Highly diverse
What would you use a tissue culture to measure? (Virology)
Cytopathic effect
Describe serology/immunological viral study
detection of antibodies to virus in blood
Give examples of serology/immunological viral methods
- haemagglutination assay
- immunofluorescence
- ELISA
Describe the structure of viruses that infect prokaryote cells
Usually have ‘naked’ capsids
Describe the structure of viruses that infect eukaryotic cells
Most often enveloped
Describe the capsid
- one or more protein subunits
- tightly packed with viral DNA
Describe virions
- have molecular receptors with varying degrees of complexity
- enable recognition of, and attachment to, host cells
From where is the envelope derived?
The host cell
What does the envelope cover?
Grace he capsid of eukaryotic viruses
Where do most DNA viruses replicate?
- In the nucleus
- They require host machinery
Where do most RNA viruses replicate?
In the cytoplasm
Describe group I viruses
- dsDNA
- must enter cell before replication
- require host DNA polymerase for genome replication
- adenoviridae, herpesviridae, papovaviridae
Describe group II viruses
- ssDNA
- most have circular genomes
- eukaryote viruses replicate in host nucleus
- parvoviridae (vertebrates), nanoviridae (plants), microviridae (prokaryotes)
Describe the mechanism by which eukaryote viruses replicate in the host nucleus
Rolling circle
Describe group III viruses
- dsRNA
- segmented genomes
- monocistronic replication
- reoviridae (rotavirus), birnaviridae
What does monocistronic replication mean?
One protein produced per gene
Describe group IV viruses
- ssRNA + sense
- mRNA directly accessed by host ribosomes to form proteins
- coronaviridae, picornaviridae (Polio)
Group V viruses
- ssRNA -sense
- genome transcribed by viral polymerases into positive reciprocal sense before translation
- paramyxoviridae, rhabdoviridae (Rabies), influenza
Group VI Viruses
- +sense ssRNA replicating through DNA intermediate
- reverse transcriptase
- splicing into host genome via integrate
- replicated using host cell machinery
- retroviruses (HIV)
Group VII viruses
- dsDNA replicate through ssRNA intermediate
- viral reverse transcriptase uses progenome RNA to produce DNA
- hepadna virus (hep B)
Describe the majority of viruses infecting bacteria and archaea
- dsDNA
- 10-100kb genome
Describe the second largest majority of viruses
ssDNA
Which type of RNA virus is common in infecting eukaryotic cells
+ sense
Which has greater diversity - eukaryote RNA viruses of prokaryote DNA viruses
Eukaryote
Describe DNA-based
genomes
- less reactive
- stable in alkaline conditions
- smaller grooves; more resistant to enzymatic attack
- mostly ds
- lower mutation rate
Why are DNA-based genomes less reactive than RNA-based genomes
- deoxyribose less reactive than ribose due to C-H bonds (not C-OH bonds)
Describe RNA-based genomes
- more reactive
- unstable in alkaline conditions
- larger grooves; more sensitive to enzymatic attack
- mostly ss
- higher mutation rate
How is phylogenetic analysis conducted on viruses?
- proteome
- no ribosomes
Proteome aka
Protein complement
Which appears to be the oldest virus group?
- dsRNA
- esp. segmented genomes
Why might DNA genomes evolve?
Protect genomes from cellular ribonuclease
Viroids
- plant pathogens
- non-protein coding RNA
- 1/80th size of viruses
How is viroid replication mediated?
host cell RNA polymerases
Interesting fact about viroids
- highest known mutation rate
- 1/400 site
As genome size increases, mutation rate
Decreases (non-linear)
Describe phage latency
prophage insertion into host genome
What controls the lytic/lysogenic state
Genetic switch
What does phage latency allow?
- long-term survival
- complex interactions of host and phage genomes
When does pseudolysogeny occur?
- nutrient deprivation
- host cannot support dna replication
Describe the lytic cycle
- Phage capsid inserts
- Capsid and tail proteins reassemble with phage genome
- Assembled phage lyses cell
Describe lysogenic state
- Phage capsid enters
- Insertion of phage genome as prophage
- Exists in dormant state
Describe pseudolysogenic state
- Phage capsid inserts
- Phage genome exists as Non-replicating preprophage
- Becomes lytic under nutrient rich
- Becomes lysogenic under nutrient poor
Mollicutes
- class of bacteria without cell wall
- Mycoplasma (several pathogenic species in humans and animals)
- undergo viral budding
What must happen to gram-negative bacteria before lysis?
- procapsid assembly
- viral genome packaging
What must happen to gram-positive bacteria before lysis?
- tail assembly
- fiber/spike assembly
Instead of lysis, gram-negative bacteria can also exit via
Viral extrusion
Describe the generalised eukaryotic virus life cycle
- Entry
- Transcription replication (mediated by viruses vs host défense)
- Assembly exit
- Virion
How might an enveloped virion enter a cell?
- attachment and fusion at the plasma membrane
- endocytosis
- apoptotic mimicry
Describe Virion endocytosis
- reception mediated: clathrin (enveloped only), caveolin, lipid, other
- macropinocytosis
How might a non-enveloped Virion enter a cell?
- endocytosis
- Pore-mediated penetration
- cell to cell transport
How might a non-encapsdiated genome enter a cell?
Cell to cell transport
Describe cell to cell transport
- syncytium
- nanotubules
- fungus hyphal anastomosis
Describe viral genome replication in eukaryotic cells
- cytoplasmic viral genome can go straight to cytoplasmic transcription and reapplication
- or nuclear transcription and replication
Describe intracellular transport
actin-dependent or microtubule-dependent
What must a cytoplasmic viral genome do to undergo nuclear transcription and replication ?
- intracellular transport
- entry into host nucleus
- integration into host chromosome
- latency
Which viruses use the peroxysome to replicate?
- tombusvirus
- spherules
Which viruses use the chloroplasm for replication?
- tymovirus
- spherules
Which viruses use the endosome to replicate?
- togaviridae
- spherules
Which viruses use the double membrane vesicles to replicate?
- arteriviridae
- coronaviridae
- flaviviridae
- picornaviridae
Which viruses use the endoplasmic reticulum to replicate?
- bromovirus
- flaviviridae
- spherules
Which viruses use the nucleus to replicate?
- baculoviridae
- herpesviridae
- polyomaviridae
Which viruses use the mitochondria to replicate ?
- nodavirus
- spherules
Which viruses use the viroplasm (of the mitochondria?) to replicate?
- poxviridae
- asfaviridae
- iridoviridae
- reoviridae
- filoviridae
Which viruses use the Golgi to replicate?
- bunyaviridae
- Tubes
How does virus assembly work if cytoplasmic transcription and replication has occurred?
- cytoplasmic capsid assembly and packaging
- (can form inclusion body)
- exit
How does virus assembly work if nuclear transcription and replication has occurred?
- nuclear capsid assembly and packaging
- (can form inclusion body)
- nuclear exit
Describe the 3 methods of virus nuclear exit
- Nuclear envelope breakdown
- Nuclear egress
- Nuclear pore export
Describe the exit strategy of a non-enveloped virion?
Lysis
Describe the exit strategy of an enveloped virion
- intracellular transoort
- budding or cell to cell transport
Describe budding
- via ESCRT
- via ESCRT-independent
Describe ESCRT
By cellular exocytosis
Describe ESCRT-independent
At plasma membrane
What happens after virion exit?
Virion maturation
What are segmented RNA viruses?
- retain distinct RNA molecules
- widespread in nature
- 11 families
Describe the 11 described families of segmented RNA viruses
- dsRNA
- ssRNA
- and - sense
What happens when two or more compatible viruses infect a cell?
- enable réassortiment and recombination of genomes
- consequences for evolution and immune escape
Describe compatible viruses
Influenza
Describe the influenza genome
- 8 segments of - sense ssRNA
- 16H segment and 9N segment subtypes
What are H segments
- HA
- bind to host cell receptors
HA
haemagglutinin
What are N segments
- NA
- facilitâtes virus exit from host cells
NA
neuraminidase
When do pandemics occur?
When viruses with new H types enter the human population by reassortment and interspecies transmission
Which strains of influenza are circulating
- H1N1
- H3N2
Which influenza strain disappeared in 2001?
H1N2
What are the strains of avian flu and what is the pathogenicity?
- H5N2 (low pathogenicity)
- H5N8 (high pathogenicity)
Which station caused the 1918 Spanish influenza and where did it come from)
- H1N1
- birds
Where and how does EBV persist?
forms a latent infection persisting in an épuisons of circular DNA within the nuclei of infected B cells
EBV
Epstein-Barr virus
How does EBV spread?
Orally; saliva
Describe EBV
- dsDNA
- 172kb genome
- Herpes family
What happens when EBV switches to lytic cycle?
- Death of infected cells
- sometimes: B cell lymphoma, Burkitt lymphoma, Hodgkin lymphoma and post transplant lymphomas
Classical Hodgkin lymphoma is characterised by
Atypical EBV associated large tumour cells
What causes post transplant lymphomas?
- suppressed T cell responses
- uncontrolled proliferation of EBV-transformed B cells
How does Burkitt lymphoma transformation occur?
- translocation of the MYC oncogene
- destructive gene mutations
ERVs
Endogenous retroviruses
What percentage of the 3 million transposable elements in the human genome are made up by retroelements
90%
What are the 2 groups of retroelements?
- Non-LTR
- LTR
Describe non-LTR retroelements
includes SINE and LINE and processed pseudogenes
SINE
- short interspersed elements
- 80-630bp
LINE
- long interspersed elements
- 6-8kbp
Describe LTR
- long terminal repeats
- includes endogenous retroviruses
How does integration of retroelements sometimes cause harm?
Disrupting or disregulating essential genes
How long is a retrotransposon?
4-8kbp
How long is an endogenous retrovirus?
9-10kbp
REV
reticuloendotheliosis virus
REV can cause
Running and tumours in poultry
Paleovirology
- the study of ancient viruses
- detected via accidental insertion into germ line of animal species, becomes EVEs
EVEs
- Endogenous viral elements
- transmitted vertically
- become ‘fixed’
What does it mean for an EVE to be fixed?
Present in all members of a species
The REV genome is more similar to
mammalian retroviruses than to other avian retroviruses
What is the reservoir host for Ebola?
Bats
What is a spillover event?
When an animal or human becomes infected with a virus from its reservoir host
How is Ebola transmitted from human to human?
Contact with blood and body fluid of sick people or Ebola cadavers
What percentage of people are asymptomatic for COVID-19?
~40%
What is the fatality rate for severe COVID?
~1%
Describe stage I of COVID symptoms:
- fever
- dry cough
- diarrhoea
- headaches
- loss of smell and/or taste
- dermal, neurological or cardiac disorders
Describe stage II of COVID
- shortness of breath
- hypoxia
- coagulation disorder
Describe stage III of COVID
- ARDS
- SIRS/shock
- coagulation disorder
- cardiac failure
Therapies for COVID
- antiviral drugs
- reducing immunosuppressive
- reducing inflammation
- anti-clotting
What does viral shedding indicate
Infectiousness
Where do the majority of emerging human viruses originate?
Other animals
What does novel infection emergence depend on?
- Contact
- Mode of transmission
- Adaptation to the new species
- Human intervention
SARS-CoV
- severe acute respiratory syndrome
- transmission of coronavirus from bats to palm civets to raccoons and ultimately humans
Compare and contrast SARS with SARS CoV-2
SARS: shedding begins 3 days after symptom onset
SARS CoV-2: shedding begins 3 days before symptom onset
Describe the Ebola virus
- filamentous virion
- sense ssRNA
- 18-19kb genome, encoding for 7 proteins
- symptoms appear 2-21 days after infection
- infects macrophages and epithelial cells
Ebola symptoms
fever -> unexplained haemorrhaging and bleeding
What is the death rate associated with Ebola bleeding and haemorrhaging ?
70-80%
EBV
Ebola virus
eVP24
- EBV protein
- prevents interferon signal (viral destruction)
Which is the most fatal Ebola virus?
Zaire Ebolavirus
How were viruses taxonomically classified back in the day?
- based on biology (informed by phenotypic data)
- wider host factors
When we say virus taxonomy was based on biological classification, what do we mean?
- in vitro properties
- virion structure
- antigenic relationships
What are the wider host factors for viral classification?
- pathogenicity
- host range
- epidemiology
How are viruses currently taxonomically classified?
- biological properties
- sequence relationships (divergence, phylogeny) -> genomic data
What is the proposed taxonomy for viruses
- phenotypes inferred from genome analysis
- sequence relatedness inferred from phylogeny, homologue detection and divergence metrics
- biological data not essential
- can be used for virus and metagenomic sequence data
APMV
- Acanthamoeba polyphaga mimivirus
- very large (visible by light microscopy)
- 1,186kb dsDNA linear chromosome
Sputnik
- 50nm icosahedral APMV-associated virus
- replicates in the virus factory of amoebae co -infected with APMV
What is the relationship between Sputnik and APMV?
- Sputnik harms APMV replication
- 70% reduction in infective APMV particles and threefold reduction in Ameoba lysis at 24hrs after Sputnik infection
What is a potential practical problem with tissue culturing?
A mono layer of tissue culture cells might curl up
Which tissue cells are usually cultured?
Sometime human, sometime chicken eggs
For a virus to enter a cell it has to
Touch it
If a virus gets into the nucleus then it has to
Get back out again
