Viruses Flashcards
What is a virion particle
Particle that is outside of the cell and moves from host to host
Viral genome may contain a lot of genes but the virion particle may only contain 1 or 2 genes
Virion particle is a simpler version of the viral genome
Ebola virus: single virion particle is enough to infect someone and has a mortality rate of 90%, but it is not that contagious
What is a virus?
A small non-cellular agent consisting largely of nucleic acid within a protein coat, requiring a host cell for reproduction
Generally not considered to be alive (still unclear)
Some studies consider viruses to be alive and that they are the 4th domain of life
Some have a very complex genome
Some viruses produce a virion factory that is a life form
Difference between a virus and a life form
Viruses are not metabolically active outside the cell
Viruses don’t have a metabolism (some viruses can change shape outside of the cell but it is not done by ATP)
Viruses assembly and life divides
Life contains ribosomes, viruses don’t
These no longer apply: All viruses thought to have capsids but some now found to not contain any, Viruses small and life big, Life large genome size and virus small
Both: Some life forms and viruses are obligate parasites
Genome diversity - viruses can be…
DNA or RNA
Double stranded or single stranded
Circular or linear
+sense or -sense (+sense viruses can be translated directly, -sense can’t be)
Segmented or non-segmented
Different genomes require different replication strategies and different life cycles
Comparison of genome size in viruses
Viruses are a lot smaller than bacteria
There are size overlaps between bacteria and viruses
Mimivirus (800,000 bp) is a very large virus
DNA vs RNA
There are RNA and DNA viruses
DNA viruses range from very small to very large
RNA viruses are a lot smaller than DNA viruses
Because RNA polymerases don’t have proofreading activity = more errors = more mutations = size limit of RNA viruses
Exception: coronavirus has genomes up to 32kb because it has a separate protein that has some proofreading activity
Overlapping genes in viruses
Viruses with small genomes have overlapping genes to save energy and allow them to be very small
Viruses have polyproteins that will be cleaved later on
Example in HIV-1 and HIV-2
HIV genomes are about 9Kb
Same segment of RNA is encoding 2 different proteins (gag and pol)
Env gene is encoding 3 separate proteins
Double and single stranded viruses
Most RNA viruses are single stranded
Exceptions are reoviruses (NOT retrovirus)
Single stranded RNA forms secondary structure (ex. Hairpins) used to control replication
Most DNA viruses are double stranded (more stable)
Exceptions are some small viruses (less than 4000bp) such as parvoviruses
Circular vs Linear viruses
Most viruses are linear, but some have circular genomes
Circular viruses replicate by rolling circle
Example: SV40 (dsDNA virus)
Discovered in the vaccine of poliovirus when tested on monkeys
Tested SV40 to see how pathogenic it was
Caused cell transformation and cancer
But doesn’t cause cancer in humans (as it undergoes abortive infection)
Negative sense versus positive sense viruses
Negative sense viruses have to produce positive sense mRNA before production of viral proteins can occur:
It is 3’ to 5’ so can’t translate it directly
Intermediate RNA is positive sense
-ve sense doesn’t contain promotors so prevents it from being transcribed
Plus sense can translate directly:
Intermediate RNA is negative sense
50/50 is a virus is positive or negative sense
Segmented viruses
Example: influenza viruses are -ve sense viruses with segmented RNA genomes
There are 7 or 8 segments depending on the virus
Influenza evolves by mutation, recombination and reassortment (co-infection of the same species and segments are reassorted into a different combination)
Non-segmented viruses
All viral RNA or DNA is encoded on one piece of nucleic acid
Example poliovirus or retrovirus
Most viruses are non-segmented (even large viruses)
Example: retroviruses have +ve sense non-segmented genomes
Evolve by mutation (from polymerase) and recombination (co-infection of a cell)
Morphological diversity of viruses
Size: viruses are usually too small to be viewed by light microscope so have to use electron microscope
Example picornavirus is a very small RNA virus
Simplest viruses - TMV
Simplest viruses have a genome surrounded by a capsid (coat)
Ex. TMV (tobacco mosaic virus in plants)
Capsid protects the nucleic acid (RNA)
Spontaneous self assembly: when a tube of viral RNA and a tube of viral capsid are mixed, get infectious viral particles
Viron particle contains only the capsid protein vs viral genome encodes 4 proteins
Virion particle is a simplified version of the viral genome
TMV is very tough outside of the host but once it is inside a tobacco plant it spontaneously disassembles
Capsid structure and assembly
Assembly of monomeric protein units can also produce spherical particles
Capsid molecules are monomers and self assemble to produce regular structures that encapsulate the RNA/DNA inside them
One or more capsid proteins can assemble into many further icosahedral conformations
Pandora virus does not have a capsid
Functions of capsid
Binds to and protects nucleic acid
forms protective shell that is stable outside of the host
recognizes host cellular receptors and allows entry of the virus into the host cell
has to disassemble easily once it is inside the host cell
involved in immune evasion to avoid antibodies
Viral envelope
Envelope surrounding the viral core
Consist of a lipid membrane (derived from the host cell)
Lipid membrane can have one or more viral envelope proteins inserted into it
Functions: binding to cellular receptor proteins, allowing fusion and entry
A lot of morphological diversity but will always have a regular structure
Host specific viruses
Some viruses are host specific ex. Smallpox and polio are human specific
Polio (small, non-enveloped, plus single stranded RNA virus)
Smallpox (large, enveloped, double stranded DNA virus)
If they are human specific that means they can be eradicated quickly
So most viruses have more than one host
What is a reservoir species
Species where the virus naturally occurs
Virus has been co-evolving with the host
Viruses in reservoir species are usually not pathogenic or are asymptomatic
Many viruses are zoonotic: an infection from a virus that has a reservoir in another species
West Nile virus reservoir species and transmission
Reservoir species is a bird
Virus can be passed from bird to bird
It is vectored by mosquitoes (virus does not replicate in the mosquito)
Humans are dead end carriers: can get infected and get ill but can’t pass it on to another species or human so transmission cycle is ended
Horses are dead end carriers and can get infected but don’t get ill
How is a reservoir species identified
Sample animals at source of outbreak
Sample animals that humans don’t have a lot of contact with as these may contribute to a new outbreak (domesticated animals would have already spread a virus)
Look at primates - have similar genomes to humans so virus is more likely to be able to replicate in humans but have low population density
Bats - social and long-lived
Rodents - large population density
Mammals in general - most of the time viruses don’t transfer between vertebrate classes (exception influenza)
Ebola viruses - finding reservoir species
Ebola outbreaks in Africa with high mortality rates but not that contagious
Build phylogenies via sequencing
Three species of fruit bats shown to have very similar viruses
Mimivirus
Contains 900 genes (next are poxviruses with 250 genes)
Genome size around 1Mbp
Blurs distinction between cellular life and viruses (as some life forms have similar or even less amount of genes)
Pandora virus is even larger (2.5Mbp)
Mimivirus gets infected by another virus (virophage called sputnik)
Stages of the viral life cycle
Infection and disassembly of the infectious viral particle
Replication of the viral genome
Transcription, translation, replication of DNA which relies on the host cell machinery (except Pox viruses which have their own replication machinery)
Synthesis of viral proteins by host cell machinery
Reassembly into progeny virus particles/maturation
Cell will fight back against the virus using defence system
Phases of viral replication (draw diagram)
Virus infects cell at time = 0
Eclipse phase: no progeny virion particles (or viral inclusion bodies) observed under microscope
Infection, disassembly, translation, transcription occurs here
Maturation and release phase: accumulation of viral particles
Takes a few hours to a few days depending on the virus
cell bursts and will lyse and progeny viruses infect new cells
Decay of progeny: not all of progeny is infectious (ex. contains mutations)
Host cell attachment
Different viruses recognize different cellular receptors on the cell surface
This determines which cells can be infected (i.e. cell or tissue tropism)
This can be very complex
Many viruses only have a single receptor
Some have 2 receptors and require both of them to be present on the cell surface
Examples of host cell attachment
Influenza A and B are RNA viruses and have receptor glycoproteins of Neu5Ac in oropharyngeal cells
Adenovirus type 2 has receptor integrins and cell type is respiratory epithelium
Poliovirus has receptor CD155 which is expressed in nerve cells which can cause paralysis
ACE2 and TMPRS2 are receptors for SARS-Cov-2
ACE2 receptor is expressed in a wide variety of tissues
Pathogenic effects of viruses are mostly accidental as it is not advantageous
HIV-1
HIV-1 is a retrovirus
HIV-1 infects the receptor CD4 (a marker of white blood cells) and CCR5 and chemokine (these are co-receptors)
HIV-1 shows cellular tropism: can switch between macrophages and T-cells during infection
Defence mechanisms in humans against viruses: example deletion in CCR5 so can’t be infected by HIV-1
Host cell infection mechanisms
A variety of mechanisms are used by different viruses to infect a host cell as a prelude to viral replication
Binding to the receptor may or may not allow entry of the virus into the host cell
Mechanisms: Fusion, endocytosis, pore formation, DNA viruses
Fusion for host cell infection
HIV-1 binds to co-receptors on the cell
Binding to receptor causes conformational change in the envelope of the virus
Causes fusion of the viral membrane with the cellular membrane
Has nuclear import factors
Endocytosis for host cell infection
Influenza binds to cell surface but there is no immediate conformational change
Binding causes cell to endocytose the virus
Virus is present in the endosome
Acidification of endosome causes conformational change
Fusion and uncoating so genomic RNA enters the cell
Has nuclear import factors
Pore formation for host cell infection
Binding of polio virus to receptor causes a conformational change
Pore forms in the membrane and viral RNA is extruded through the pore
Virus replicates in the cytoplasm
DNA viruses host cell infection
Adenovirus binds to receptors on cell
Endocytosis of virus into the cell
Trafficking into the nucleus via nuclear import factors
DNA viruses always replicate in the nucleus
Where does replication of viral genome occur?
Most DNA viruses replicate in the nucleus (except poxviruses)
Most RNA viruses replicate in the cytoplasm (except influenza and others)
Retroviruses are an exception as they are RNA that are reverse transcribed into DNA (exist as DNA in the cell)
Viral replication of ssRNA+
RNA enters the cell
Translation is direct
Production of viral polymerase and capsid
Polymerase starts genome synthesis
All RNA viruses have a gene encoding RNA polymerases
Can’t use host RNA polymerase as host RNA polymerase is DNA directed
RNA polymerase uses +sense RNA to make -sense RNA which is used to make more +sense RNA
Replitative form (RF) form: intermediate form of double stranded RNA
This is sensed by the host cell to turn on defence mechanisms
Viruses hide double stranded RNA ex. in a vesicle to prevent host cell from sensing it
Spontaneous assembly of capsid and RNA, occurs at the site of replication
Viral replication of ssRNA-
Genome is antisense to mRNA so can’t be translated
Virion particle contains RNA dependent RNA polymerase to synthesize mRNA
Viral RNA polymerase uses -ve sense RNA to make + sense RNA and polymerase then synthesizes - ve sense RNA
Assembly of capsid, RNA and a polymerase
If doesn’t contain a polymerase, it is not infectious
Viral replication of dsDNA
Must replicate in the nucleus
Imported into nucleus using nuclear import factors
Transcription, translation
Produces DNA polymerase allowing for DNA replication
Most viruses contain a DNA polymerase but may not have all of the proteins required for replication so rely on the host nucleus
Except Pox viruses that contain all of the replication proteins so can replicate in the cytoplasm
Viral replication of retroviruses
Viruses exist as RNA in the virion particle
Switch from RNA to DNA during their life cycle
Retrovirus is imported into the nucleus via nuclear import factors
Reverse transcription from ssRNA+ to dsDNA (provirus) using reverse transcriptase (reverse transcriptase is RNA or DNA directed)
Integrase integrates the DNA into the host cell
Host cell takes over transcription, translation and assembly
Host proteins and viral replication
Transcription uses host polymerases
Replication uses viral polymerases
Many host transcription factors bind to viral RNA (thus increasing/controlling expression)
Translation uses host ribosomes
Viral polypeptides often cleaved by host proteases
Influenza replication
Influenza (-ve sense) doesn’t have a cap or poly-A tail when +sense is made
Influenza steals the caps from host RNA which allows influenza RNA to be translated and prevents host RNA from being translated
Viral replication is often dependent on the state/condition of the host cell
Capsid and virus assembly
Capsid assembly generally occurs at the site of genome replication
Often self assembly with simultaneous binding of viral genome to the capsid protein
Viruses with envelopes are assembled either on the surface of the cell or in sub-cellular compartments
Viral membrane is derived from the host cell
Surface assembly of viruses with envelopes
Capsid and nucleic acid partly assembles in cytoplasm and finished off on cell surface
Viral envelope proteins are trafficked to cell surface
Interact with core of the virus which causes budding through the cell to get progeny virus with an envelope
Cell can produce progeny virus without disrupting its own membrane
So envelope viruses usually have a slow release of viral release
Non-envelope viruses usually kill the cell
Permissive cells
Cells supporting viral infection are permissive
Virus infects a cell and progeny virus particles come out
Completes viral life cycle inside the host cell
Gives rise to productive infection producing virion particles
Production of virion particles gives cytopathic effects which are damaging to the host cell (ex. death)
Acute infection
Cell dies or cell survives
Quick infection
RNA viruses are acute (except retroviruses which become DNA)
Non-permissive cells
Infection of non-permissive cells leads to abortive or restrictive infection
Virus enters the cell but no viral particles come out
Cell is fighting back against viral infection
Prevents virus from completing its life cycle
Can cause cell transformation and can lead to oncogenesis
Example SV40 in guineapigs and rodents
Persistent infections
Are latent or chronic
Chronic: Slow and low infection. Infections lasts for a long time but don’t produce a lot of virus
Latent: Virus may not produce any viral particles. Example HIV has reservoir cells in which they persist. Can reappear at a later time (example chickenpox). Are often DNA viruses or retroviruses
Oncogenic viruses
Transformation of cells
Often retroviruses
Example SV40 can cause cancer
Most of the time cell transformation is accidental
Example papilloma virus can cause cervical cancer
Morphological effects of viruses on cell
Changes to nucleus (nuclear inclusion), cytoskeleton, giant cell formation
Due to build up of viral particles which forms inclusion bodies
Or due to viral trafficking in host cell
Some plant viral inclusion bodies have evolved not to cause any stress to the host cell
Envelope viruses interaction with host cell
Envelope viruses allow fusion of virus to a host cell
Causes fusion with an uninfected cell to give multinucleated syncytia
Measles and retroviruses
Viral envelopes have been co-opted by humans and are a benefit to us (find multinucleated syncytia in the placenta)
Effects of viruses on cell biochemistry and physiology include:
Activation of cellular protein kinases and transcription factors
Activation of cellular oncogenes, cell cycle arrest
Example Viruses arrests cell cycle in the S phase and shuts down host replication to only allow its own replication
Inhibition of DNA synthesis
Large dsDNA viruses cascade model of viral replication
Example CMV (cytomeglavirus)
Has waves of viral proteins being produced
Called the cascade model of viral replication
Cytopathic effects occur at the last stage before the cell bursts
CMV has a slow life cycle
Genetic effects of viruses on host cells
Genetic effects on host cells include transformation
Generalised chromosomal damage
Example: a virus doesn’t undergo through all of life cycle (abortive)
It is replicating in the nucleus which causes chromosomal damage and cell transformation leading to cancer
Induced defence against viral infection
Cells recognize double stranded RNA
Turn on their defence mechanism
Interferon is expressed and secreted by infected cells in response to double stranded RNA
Interferon signals uninfected cells that a virus is present and stimulates antiviral defences
Interferon makes many antiviral proteins to target many different stages of the viral life cycle
So prevents resistance of a virus to proteins
Example of induced defence with T.I.P
Interferon makes T.I.P (translation inhibitory protein)
T.I.P binds to ribosomes so it is slower at translating RNA
So allows ribosome to make sure RNA is a host RNA
Example viral RNA does not have a proper cap on it
Example influenza steals host caps so it is translated
Influenza subverted aspect of the TIP defence mechanism as host RNA won’t get translated now
Example of induced defence with TRIM5
Induced by interferon
TRIM5 blocks disassembly of viruses once they enter the cell
Example of induced defence with Tetherin
Induced by interferon
Tetherin tethers the virus to the cell surface
It has a transmembrane region and a GPI-anchor
It can insert into two different membranes
So prevents virus from leaving the cell
Non-induced/innate defences against viral infection with APOBEC3G
Non-induced defence varies from tissue type to tissue type
Some tissues may not be permissive for viral infection
APOBEC3G defends against retroviruses
Incorporated into the virion particle during infection
When the next cell is infected, APOBEC3G deaminates dC to dU on the minus strand so doesn’t have any G on the + strand
HIV has overcome this defence by acquisition of the vif (viral infectivity factor) gene
Rous sarcoma virus
Rous Sarcoma virus (RSV) is a muscle cancer
It is a retrovirus
Can transform cells because it has captured an oncogene by insertion into the viral genome during viral replication
Showed that cancers can be transmissible
When cell is infected by RSV produces a lot more viral particles
Viruses related to RSV (termed ALVs) do not contain oncogenes
So both infect chickens but only RSV transforms chicken cells
HPV infection mechanism
Epithelial cells are infected first
Then basal cells are infected
Virus is not producing viral particles at this stage
Only produces viral proteins at the top of the epithelial layer
Virus replicates as an episome
An episome is viral DNA that is separate from the nucleus (When cell divides episome also divides)
HPV affecting Rb1 and P53
Rb1 and P53 are host tumour suppressor genes that are downregulated by HPV
Many DNA viruses downregulate Rb1 and P53
But most of the time this doesn’t cause cell transformation
Because genes that regulate Rb1 and P53 are under tight regulation by the virus itself so they are not overexpressed
Infection by HPV causes accidental integration of part of the virus into a host cell. The integrated genes are involved with regulating Rb1 and P53 leading to overexpression and cervical cancer
Morphology of coronaviruses
Enveloped ssRNA virus
Two or more envelope proteins
Spike glycoprotein on virus binds to ACE2 receptor in humans
Odd-shaped core in a helical arrangement
Taxonomy and phylogenies of coronaviruses
Different subfamilies of coronavirae: alpha, beta, gamma, delta virus genera
Mainly interested in the different beta CoVs (and a bit on the alpha CoVs)
Multiple human coronaviruses exist
Some are non-pathogenic
SARS-2 and MERS have a high mortality rate and are pathogenic
What is MERS?
Has seasonal outbreaks in the middle east
Middle east respiratory system
Is pathogenic
Has a Camel reservoir
What is surprising about coronaviruses?
They are very plastic in changing their receptor targets frequently
Example changing tissues and hosts they infect
Rapid horizontal transmission
SARS-2 only appeared in 2020 and it is already affecting more than 1 dozen different species
What is SARS-CoV2?
Variant of original SARS-CoV
Natural reservoir is a bat
Both are closely related to viruses in bats
Bats are very common reservoir hosts for human viruses (ex. ebola)
Both have intermediate hosts (SARS-CoV=Civet and SARS-CoV2=Pangolin or racoon dogs)
Life cycle of coronaviruses
Typical +ve sense RNA virus life cycle
Subsurface assembly in a vesicle and exocytosis (uncommon for a virus as usually released via budding)
This is SARS-CoV but SARS-CoV2 is very similar
Genomic organization and size of coronaviruses
Coronaviruses are much bigger than other RNA viruses (but a lot smaller than many dsDNA viruses)
Very big genome due to ExonN that allows proofreading activity of the polymerase complex
Proofreading activity works against missense mutations but not deletions or insertions
Has structural proteins (ex. spike-glycoprotein)
Many other accessory proteins involved in combatting the host immune/antiviral response which is unusual for a virus
Reproductive numbers in SARS-Cov1 and SARS-Cov2
SARS-Cov1 had a reproductive number between 2-5
SARS-Cov2 had a reproductive number of 3
SARS-Cov1 occurred in April 2003 and then decreased in summer so got no pandemic
SARS-COV2 occurred in December
SARS-Cov-2 every new variation has a higher reproductive number so becomes more contagious
Mortality of SARS-CoV1 around 10%, causes severe injury to lungs
Reproductive number
The higher the reproductive number the more contagious the virus is
Low reproductive number means virus is affected by seasonal variation (temperatures)
Increasing heat decreases reproductive number
Influenza is low enough that in the summer, reproductive number drops below 1
Measles is the highest (12-18) so it is very contagious
SARS-CoV2 Spike mutations
Very plastic virus that can easily infect a lot of species
Due to spike like protein that picks up mutations
These mutations benefit the virus
Example allow it to become more specific, bind faster to the receptor or allow immune escape
Variants of SARS-CoV2
Get waves of variants occurring
Delta and omicron variants are very different
Usually COVID is the result of an acute infection (either die or clear it)
But some individuals become a chronic infection (example individuals that are immune suppressed)
Variants come from long incubation with a particular individual
Seasonality and the Kent (UK) variant
SARS-Cov2 arised in December
In absence of a lockdown, reproductive number is lowest when the temperature is high and when the population density is low
In summer 2020 Covid was lowest as viruses don’t persist well in environment when it is hot and humid
But because many different variants arised that had higher reproductive numbers, summer and hot temperatures did not help
Routes for virus infection
Virus has a Route of entry, target organ, route of exit, infection of other individuals
Respiratory tract (influenza)
Oral cavity (hep A uses this route)
Genital tract (ex. HIV)
Skin (ex. rabies, yellow fever)
SARS2: site of entry is mouth and replicates in pharyngeal tube
Viral spread and pathogenesis cycle
Primary viremia at the site of entry: get some viral replication but usually no symptoms
Dissemination through the body via circulatory systems or nerve systems
Moves to target organ and causes secondary viremia and disease
Pathogenesis occurs by direct cytopathic effects on cells (Virus kills so many cells that the body can’t replace)
Virus moves to site of shedding leading to spread in environment
Dissemination in blood examples and examples of viruses
Smallpox and measles
Smallpox target organs: Respiratory mucosa, spleen, bone marrow, lymph nodes
Measles target organs: Lymphatic and respiratory systems, skin, brain
Measles implantation site, and route of spread
Site of implantation: respiratory tract
Route of spread: blood
Target organs: skin, lungs, brain
Site of shedding: respiratory tract
Rabies implantation site, and route of spread
Site of implantation: bite
Route of spread: nerves
Target organs: brain
Site of shedding: salivary glands
Dissemination in nervous system
Nervous system can also disseminate viruses by similar mechanisms as blood
Rabies and herpesviruses
Rabies hijacks the nerve cell transport system
Rabies does not lyse cells, most of the time the inflammatory response kills the individual
Dissemination in plants
Thin membrane that can be penetrated
Has a circulatory system
In an animal, local spread would be along mucus membranes but plants have cell walls instead
So plant virus must move from cell to cell via a different mechanism
Cytoplasmic connections called plasmodesmata
Viruses have movement proteins
Movement proteins forms complex with viral RNA
Viral RNA MP complex moves through to plasmodesmata
Binds to cell surface which widens it out (called gating)
Afterwards plasmodesmata shuts again
Viral persistence in organism
Virus is not cleared from the organism
Involves modulation of virus (slowing replication) and cell/host immune response
Persistent infections can be latent and then become reactivated (example by stress, UV light, infection by another virus)
Persistent infections are often found by viruses infecting the immune system, nervous system or digestive system
These are latent reservoirs: virus needs to find a place to hide from the immune system where immune surveillance is low
How do viruses escape the immune system?
Avoidance of neutralising antibodies by spreading directly from cell to cell
Example HIV is not expressing any protein so immune system can’t mark a cell as infected/T-cell won’t recognize it
Budding into cytoplasmic vacuoles
Genetic variation (quasispecies - a range of slightly different viral sequences)
Inhibition of immune and nonspecific defences
Becoming latent
Episomal vs integrated virus genomes
Viruses can be integrated into cell DNA or be an episome
Episome is a piece of DNA that is replicating independent of the host chromosome
Epstein Barr virus (EBV)
Has 3 versions of latency
It is an example of a virus maintained in the immune system
EBV replicates as an episome
EBNA (EBV nuclear antigen) maintain viral DNA and the episome allowing long term persistence
LM protein (latent membrane protein) downregulate viral expression
Retroviruses are integrated into the DNA so don’t need any viral proteins
Herpes simplex virus
HSV is an example of a virus maintained in the nervous system
Nerves are protected from immune surveillance as immune system will not kill nerve cells
Causes a cold sore, then immune system gets rid of it, get repeated waves of infection
General host defences against viral infection
Several types of defence including non-specific defences and induced defences
Non-specific defences: Anatomic barriers (skin), non-specific inhibitors, fever and inflammation
More specific defences: NK cells and interferon production
Fever and inflammation as a defence against viral infection
Not caused by the virus, caused by the bodies defence to the virus
Viral replication is lower at higher temperature, so fever prevents virus from replicating quickly
Fever and inflammation is a way of recruiting antiviral cells to site of infection
Interferons
Turn antiviral defences of uninfected cells on
Increases MHC1 cell expression and antigen presentation on in all cells (uninfected and infected)
MHC1 is recognized by T-cells
Lead to activation of natural killer (NK) cells to kill virus infected cells
Natural killer cells
NK cells are non-specific
First line of defence of killing virus infected cells
Afterwards get adaptive immune response by B and T cells
NK cells are killing enough virally infected cells to stop increase of virus titer until adaptive immune system comes in
MHC-1 expression
MHC-1 presents intracellular fragments to T cells to allow monitoring of internal contents of cell
Healthy cells express MHC-1 presenting normal peptides to T-cells
Virus alters expression of MHC-1 for immune evasion
Healthy cell that has MHC-1 = NK cell does not kill cell
Cell that has no MHC2 = NK cell kills it
