Virus Properties Flashcards
How are Viruses Named
AFter geographic locales
Viruses Can infect bacteria: Bacteriophages
Gut virome is largely unexplored
Bacteriophage outnumber bacteria in the gut
- could be indicators of microbiome health
- could be used to alter microbiome therapeutically
- phases for food safety
- phases as biomarkers of health/disease
- phases as reporters of microbiome diversity
- phases for disease therapy
- phases as drivers of microbiota
- phases as delivery vectors
Plant Viruses
Viruses can also infect plants
Fungi are most important plant pathogens with viruses coming in second
Virus Eradication through Vaccination
Smallpox
Rinderpest
Polio (soon)
If a virus only infects humans (like measles) and there is a good vaccine (Eg measles) then the virus can theoretically be eradicated through mass vaccination
History and important
Viruses in the 1860s Pasteur speculated about a pathogen too small to be detected with a microscope
1931 first images of viruses with electron microscopy
SARS, west Nile, influenza, Influenza, Ebola, enterovirus, Zika
- viruses are most abundant biological entity on early (10x higher than bacteria)
- major cause of human disease
- can cause cancer
- new viruses emerge all the time
- bacterial viruses help to move genetic information between bacteria increasing spread of drug resistance and affecting pathogenesis
- now we have antivirals
Virus size
100-1000x smaller than cells
<100nM in diameter or less
Smaller than RBC!!
Filamentous viruses like Ebola can be long and threadlike with lengths up to 1000 mm
Largest known infects algae and is 1/4 size of ecoli
Properties of Viruses
Contain DNA or RNA genome (never both)
No protein synthesis machinery (no ribosomes)
No energy generating machine
Nucleic acid enclosed in a protective coat (capsid)
Viral replication has two phases
- outside host: inert collection of macromolecules called a virion
- inside host: utilize host cell machinery to copy self and produce more virus
Do not grow or undergo division, assembled from pre-formed components
Obligate intracellular pathogens NO EXCEPTIONS
Basic Virus Structure
Protein shell (capsid) surrounding nucleic acid genome –> full assembly is called a nucleocapsid
Enveloped viruses have lipid membrane surrounding nucleocapsid
Naked or non-enveloped viruses have no membrane
Projections from surface of virion (spikes or envelop proteins) serve as sites of attachment to receptors on host cells
Virus Classification
DNA vs RNA **
Morphology
Presence or absence of envelope **
Ds or ss genome, genome segmented or not
Practical implications of RNA vs DNA genomes
RNA dont have proof reading functions so they mutate more than DNA viruses
RNA viruses replicate quickly, particularly + RNA viruses, since their genome is in effect mRNA
–> do not cause chronic infections
Genome Size
Ranges from 2000 bp to 800,000 basepairs, super small! Depend on host cell p athways
- dont have to make ribosomes
- when viruses have larger genomes they encode proteins that modulate host in some way
How do viruses conserve genetic space?
- Polyprotein production
- make polyprotein that is cleaved by a viral or cellular protease eg least efficient way for a virus to code for proteins is to have a separate gene for each with each gene having its own promoter so the polyprotein is cleaved by a viral protease resulting in production of final p rotein products
- clinically protease inhibitors used to treat HIV and hepC –> block viral polyprotein cleavage - RNA splicing
- same promoter, just splice things together - Overlapping Reading frames (and splicing)
- single promoter with overlapping reading frames
- when coupled with mRNA splicing, you again get different proteins produced via a common promoter
- given nucleotide may play a role in encoding two or even three different viral proteins - Ribosomal frame-shifting
- while scanning along mRNA ribosome will slip back one base and then continue again–> frameshift and production of a different protein
Capsid Functions
Capsid can have an icosahedral or helical shape
Packing or condensation
Protection of nucleic acid
Transport nucleic acid from cell to cell
Provides specificity for attachment
Metastable:capsid undergo changes that result in delivery of the genetic material into a cell (for a virus to infect a cell, it has to deliver its genome into the cytoplasm of the cell)
Virus Membranes
Some viruses consist of only a capsid (polio, hepatitis A, rhinoviruses)
Some viruses surround their capsids with a lipid membrane:
- all helical capsids are membrane enveloped (rabies, Ebola, flu)
- some icosahedral capsids are membrane enveloped (west Nile virus, yellow fever)
- since viruses cant make their own membranes they steal membrane from the cell through a process called budding
Budding
The process in which a viral matrix protein steal membrane from the cell to go from virion in the cell to free infection virion with a membrane around it
These have spike proteins which mediate attachment of virion to the host cell
Maturation and Budding of enveloped virion
- viral capsid assembles in the cytoplasm
- virus also makes one or more integral membrane proteins (the spike or envelope protein)
- capsid interacts with cytoplasmic domain of viral glycoproteins and zippers up
- virus buds from cell surface, pinching off and forming a new virus particle
- host cell proteins are excluded from the budding virus particle
**budding normally occurs at cell surface, but some viruses bud from ER (west Nile, hep B) and others from the golgi (Rift Valley river)
Spike Proteins
Enveloped proteins have one or more, they attach a virus to cell surface, get virus into cell, and are targets for antibodies
How does the envelope affect transmission?
Presence or absence of an envelope affects transmission
- enveloped viruses = HIV, hepB, influenza, herpes simplex, Ebola and are spread by body fluid and are stable outside the body
- enveloped viruses have lipid membranes that are stable making them very sensitive to osmotic stress, desiccation, and extremes of pH and salt so viruses surrounded by lipid membranes are transmitted by transfer of body fluids eg sexual transmission
non enveloped
- way more stable outside human body, can be transmitted by other mechanisms eg fecal-oral route (how polio and many other GI viruses are transmitted) eg rhinovirus, hepatitis A, polio
Not inactivated by ether (70% ethanol), simple soaps or Lysol but enveloped viruses are
Does Purell work?
Only against enveloped viruses like influenza, hepB, herpes simples 1 and 2 but less effective in controlling transmission of human enteric viruses
What should we know about viruses
DNA vs RNA
Genome segmented? Eg influenza
Plaque Forming Units PFU
Way to measure virus in solution
Virus solution is serially diluted and placed on a monoolayer of cells growing in a dish, if virus lands on and infects a cell, new viruses will be made and these will infect adjoining cells
In 2 - 3 days monolayer will develop holes in it or plaques which you can see and count
Number of plaques correlates to number of infectious viruses–> can determine how much infectious virus you have
Viral Titer During a Single Cycle of Viral replication
PFU vs time,
Eclipse phase: attachment, disassembly (at first PFU goes down as the virus you add binds to and infects the cells), replication all intracellular, between start of infection and when the first progeny virus emerge
Post eclipse phase, PFU ^^ viruses are being made and released from infected cells
Virus Lifecycle
Attachment Penetration Uncoating Translation, Transcription, Replicatin Assembly Release
Attachment
Virus binds to a specific receptor, and the presence or absence of these receptors dictates virus tropism (ability of virus to infect some cell types not others)
Viral receptors are host cells that
- bind virus to cell (nonenveloped - bind capsid; enveloped - bind glycoprotein, receptor binding protein)
Act to tether virus
Trigger conformational changes in capsid or glycoprotein needed for entry
Send signals to cell that in some way prepare it for infection - i e the virus induces the cell to become a more permissive host
Receptors usually host surface proteins, sometimes carbs
Penetration
Virus has to get inside cell - OBLIGATE INTRACELLULAR PARASITES - must find a way to get their genetic material into the cytoplasm because they cannot replicate in a vacuole like some bacteria and parasites
- some endocytosed
- enveloped viruses cause fusion between their membrane and that of the cell
- nonenveloped viruses either make a pore or actually disrupt the membrane
Three main ways to penetrate
- membrane fusion (enveloped) (attachment, receptor engagement, trigger event pH dependent or independent, conformational change, membrane fusion)
- pore formation (non enveloped) low pH in endoscopes induces conformation change in capsid proteins such that hydrophobic domains are exposed and insert into endosomal membrane forming a pore, viral DNA or RNA enters via the pore eg poliovirus
- membrane lysis (nonenveloped–> enter cells by endocytosis then lyse vacuole and escape to cytoplasm)
Uncoating
Viral genome is tightly compacted within capsid, so capsid has to uncoat for replication to proceed
Translation, transcription, replication
Make viral proteins, make viral RNA, replicate viral genome to make new viruses
Assembly and RElease
Put viral proteins, RNA and genome together to make new virus particles
Viral Tropism
Tropism: spectrum of tissues and cell types infected by a given virus
Some viruses have very restricted tropism, others broad
Explained by presence or abscence of viral receptor
Each type of virus binds to one receptor to attach to cell surface, initiating entry process
How do different viruses replicate their genomes
DNA genomes - large viruses (pox-, herpes-) encode enzymes required (eg DNA polymerase) and are more autonomous
- small viruses use host cell polymerase and other enzymes and DNA synthesis is inside the nucleus
RNA genomes - encode their own RNA dependent RNA polymerase, which uses complementary RNA as a template
Retroviruses (and HBV) copy a ss+ RNA genome into dsDNA which is the template for new genome synthesis
Key point: RNA dependent polymerase lacks proofreading and so RNA viruses mutate quickly and replicate faster
Replication strategy of negative stranded RNA viruses
Carry their own polymerase because it is the only way they can make + RNA copy of their -RNA genome
- need RNA-dependent RNA polymerase (RDRP incorporated into virion) then they make +RNA (mRNA) and can make viral proteins, viral RNA polymerase, - RNA
STrategy of positive stranded RNA viruses to replicate
Viral polymerase not in virion, viral RNA alone is infection and the intiial event in cell si translation
Vs -RNA has a viral polymerase, is non infectious and the initial event is transcription
Mechanisms of virus mutation
Simple mutation - during replication the wrong base pair is used (happens in ppl too but slowly bc DNA polymerase have low error rate and proof reading)
Recombination - crossing over with DNA viruses
Reassortment - viruses with segmented genomes… if two viruses infect same cell and replicate, genetic segments can get all mixed up, are reassorted–> rapid generation of a new type of virus
Point mutations
Viruses grow rapidly
Single particle makes a lot of progeny
DNA viruses seem to have access to proof reading and have a low mutation rate
RNA viruses dont have proof reading so they often have a high mutation rate
REcombination
Common in DNA viruses
Reassortment
Form of recombination (non classical)
Efficient
Segmented virus only
How do pathogens share genetic material
Bacteria:
Conjugation - sex pilus between bacteria
Transformation - bacteria take up naked DNA
Transduction - DNA delivered by bacteriophage
Viruses
Recombination- exchange of DNA by crossing over
Reassortment - segments get mixed up
Virus Assembly
Formation of individual structural units of protein shell from one or several viral proteins–> assembly of the protein shell by appropriate and sometimes variable interactions among structural units–> selective packaging of nucleic acid genome and other virion components–> acquisition of an envelope–> release from host cell–> virion maturation
How does virus selectively package its own RNA or DNA and not cellular molecules?
Viral genomes hav epackaging signals that are recognized by viral proteins with particular secondary structures
This is useful! Bc it enables you to make a gene therapy vector: place the packaging signal upstream of your gene of interest; resulting RNA (or DNA) will be packaged into your virus and function as the payload but there is no new virus created because it lacks the real viral genome
What are the two common mechanisms which virus is released from cells
Enveloped viruses: bud from a cellular membrane
Non enveloped viruses: accumulate in the cell, released when the cell dies and is lysed
Burst size = avg number of virus particles released from an infected cell
