Viruses

Question 1

What is a virion particle

Answer 1

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

Question 2

What is a virus?

Answer 2

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

Question 3

Difference between a virus and a life form

Answer 3

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

Question 4

Genome diversity - viruses can be…

Answer 4

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

Question 5

Comparison of genome size in viruses

Answer 5

Viruses are a lot smaller than bacteria
There are size overlaps between bacteria and viruses
Mimivirus (800,000 bp) is a very large virus

Question 5

DNA vs RNA

Answer 5

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

Question 6

Overlapping genes in viruses

Answer 6

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

Question 7

Double and single stranded viruses

Answer 7

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

Question 8

Circular vs Linear viruses

Answer 8

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)

Question 9

Negative sense versus positive sense viruses

Answer 9

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

Question 10

Segmented viruses

Answer 10

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)

Question 10

Non-segmented viruses

Answer 10

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)

Question 11

Morphological diversity of viruses

Answer 11

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

Question 12

Simplest viruses - TMV

Answer 12

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

Question 13

Capsid structure and assembly

Answer 13

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

Question 14

Functions of capsid

Answer 14

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

Question 15

Viral envelope

Answer 15

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

Question 16

Host specific viruses

Answer 16

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

Question 17

What is a reservoir species

Answer 17

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

Question 18

West Nile virus reservoir species and transmission

Answer 18

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

Question 19

How is a reservoir species identified

Answer 19

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)

Question 20

Ebola viruses - finding reservoir species

Answer 20

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

Question 21

Mimivirus

Answer 21

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)

Question 22

Stages of the viral life cycle

Answer 22

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

Question 23

Phases of viral replication (draw diagram)

Answer 23

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)

Question 24

Host cell attachment

Answer 24

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

Question 25

Examples of host cell attachment

Answer 25

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

Question 26

HIV-1

Answer 26

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

Question 27

Host cell infection mechanisms

Answer 27

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

Question 28

Fusion for host cell infection

Answer 28

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

Question 29

Endocytosis for host cell infection

Answer 29

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

Question 30

Pore formation for host cell infection

Answer 30

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

Question 31

DNA viruses host cell infection

Answer 31

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

Question 32

Where does replication of viral genome occur?

Answer 32

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)

Question 33

Viral replication of ssRNA+

Answer 33

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

Question 34

Viral replication of ssRNA-

Answer 34

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

Question 35

Viral replication of dsDNA

Answer 35

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

Question 36

Viral replication of retroviruses

Answer 36

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

Question 37

Host proteins and viral replication

Answer 37

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

Question 38

Influenza replication

Answer 38

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

Question 39

Capsid and virus assembly

Answer 39

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

Question 40

Surface assembly of viruses with envelopes

Answer 40

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

Question 41

Permissive cells

Answer 41

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)

Question 41

Acute infection

Answer 41

Cell dies or cell survives Quick infection RNA viruses are acute (except retroviruses which become DNA)

Question 42

Non-permissive cells

Answer 42

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

Question 43

Persistent infections

Answer 43

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

Question 44

Oncogenic viruses

Answer 44

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

Question 45

Morphological effects of viruses on cell

Answer 45

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

Question 46

Envelope viruses interaction with host cell

Answer 46

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)

Question 47

Effects of viruses on cell biochemistry and physiology include:

Answer 47

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

Question 48

Large dsDNA viruses cascade model of viral replication

Answer 48

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

Question 48

Genetic effects of viruses on host cells

Answer 48

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

Question 49

Induced defence against viral infection

Answer 49

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

Question 50

Example of induced defence with T.I.P

Answer 50

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

Question 51

Example of induced defence with TRIM5

Answer 51

Induced by interferon TRIM5 blocks disassembly of viruses once they enter the cell

Question 52

Example of induced defence with Tetherin

Answer 52

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

Question 53

Non-induced/innate defences against viral infection with APOBEC3G

Answer 53

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

Question 54

Rous sarcoma virus

Answer 54

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

Question 55

HPV infection mechanism

Answer 55

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)

Question 56

HPV affecting Rb1 and P53

Answer 56

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

Question 57

Morphology of coronaviruses

Answer 57

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

Question 58

Taxonomy and phylogenies of coronaviruses

Answer 58

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

Question 59

What is MERS?

Answer 59

Has seasonal outbreaks in the middle east Middle east respiratory system Is pathogenic Has a Camel reservoir

Question 60

What is surprising about coronaviruses?

Answer 60

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

Question 61

What is SARS-CoV2?

Answer 61

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)

Question 62

Life cycle of coronaviruses

Answer 62

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

Question 62

Genomic organization and size of coronaviruses

Answer 62

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

Question 63

Reproductive numbers in SARS-Cov1 and SARS-Cov2

Answer 63

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

Question 64

Reproductive number

Answer 64

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

Question 65

SARS-CoV2 Spike mutations

Answer 65

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

Question 66

Variants of SARS-CoV2

Answer 66

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

Question 67

Seasonality and the Kent (UK) variant

Answer 67

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

Question 68

Routes for virus infection

Answer 68

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

Question 69

Viral spread and pathogenesis cycle

Answer 69

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

Question 70

Dissemination in blood examples and examples of viruses

Answer 70

Smallpox and measles Smallpox target organs: Respiratory mucosa, spleen, bone marrow, lymph nodes Measles target organs: Lymphatic and respiratory systems, skin, brain

Question 71

Measles implantation site, and route of spread

Answer 71

Site of implantation: respiratory tract Route of spread: blood Target organs: skin, lungs, brain Site of shedding: respiratory tract

Question 72

Rabies implantation site, and route of spread

Answer 72

Site of implantation: bite Route of spread: nerves Target organs: brain Site of shedding: salivary glands

Question 72

Dissemination in nervous system

Answer 72

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

Question 73

Dissemination in plants

Answer 73

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

Question 74

Viral persistence in organism

Answer 74

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

Question 75

How do viruses escape the immune system?

Answer 75

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

Question 76

Episomal vs integrated virus genomes

Answer 76

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

Question 77

Epstein Barr virus (EBV)

Answer 77

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

Question 78

Herpes simplex virus

Answer 78

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

Question 79

General host defences against viral infection

Answer 79

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

Question 80

Fever and inflammation as a defence against viral infection

Answer 80

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

Question 81

Interferons

Answer 81

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

Question 82

Natural killer cells

Answer 82

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

Question 83

MHC-1 expression

Answer 83

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