ICL 1.1: Intro to Viruses

Question 1

What are the 3 components of medical virology?

Answer 1

1. infectious agent
2. health interventions
3. host defenses

Question 2

what are the categories of infectious agents?

Answer 2

1. viruses
2. bacteria
3. fungi
4. protozoa
5. animalia

Question 3

what is a virus?

Answer 3

obligate intracellular parasites

small, obligate intra-cellular parasites, possessing either a RNA or DNA genome and a receptor-binding protein (capsid/coat) allowing entry into cells

Question 4

where do viruses replicate?

Answer 4

they replicate only inside the living cells

this is because they use the cellular synthetic machinery for transcription, translation and replication to cause the synthesis of specialized elements called virions that serve to transfer the viral genome, which can be either RNA or DNA, to other living cells

if you put a virus in a petri dish, nothing will happen!

Question 5

is the viral genome RNA or DNA?

Answer 5

DNA or RNA: it can be either!!

viruses use cellular machinery to synthesize virions that serve to transfer the viral genome, which can be either RNA or DNA, to other living cells

**there are no bacteria with RNA genomes

Question 6

what is the infectious form of a virus called?

Answer 6

virion

virions are either enveloped or non-enveloped (naked)

Question 7

what are the 2 distinct stages/forms of a virus?

Answer 7

1. non-infectious form = virion

2. non-infectious form of virus = intracellular form of virus represented by its genome

Question 8

what are the components of a virion?

Answer 8

1. genome
2. capsid
3. matrix
4. envelope

Question 9

what are the two types of virions?

Answer 9

virions are either enveloped or non-enveloped (naked)

enveloped viruses are sensitive (inactivated) to
organic solvents, detergents

Question 10

what inactivates enveloped viruses?

Answer 10

enveloped viruses are sensitive/inactivated to organic solvents/detergents

Question 11

what is the capsid of a virion?

Answer 11

a protein shell that surrounds the genome

the RNA and DNA need to be protected so viruses make a protein shell to protect it

a capsid can have many shapes!

Question 12

what are the types of capsidss?

Answer 12

1. cubic (icosahedral)
2. helical
3. complex

Question 13

what is the matrix of a virion?

Answer 13

matrix proteins are extra proteins put into the virus that help with infection or boost the replication cycle

they’re proteins inbetween the capsid and the envelope

not all viruses have a matrix!

Question 14

what is the envelope of a virion?

Answer 14

its a lipid bilayer with a glycoprotein external layer surrounding nucleocapsid

enveloped viruses have a lipid bilayer outside the capsid protein that contains the viral envelope proteins (these have receptor-binding functions)

some viruses have envelopes and others don’t – viruses without envelopes are called naked

so it goes genome –> capsid –> envelope from inside out

Question 15

what is a nucleocapsid?

Answer 15

genome + capsid

Question 16

can you tell which virus something is from the microscope image?

Answer 16

not always

sometimes the image is diagnostic like with HIV because it’s really distinct

but other times you can’t because like influenza looks like Ebola

so images can be helpful but not always

Question 17

what is the name of the viral structure composed of

the genome enclosed in a protein coat?

Answer 17

nucleocapsid

genome + protein shell

the nucleocapsids of viruses without envelopes are the virion structures of these viruses (also called naked virions)

Question 18

list the DNA virus families

Answer 18

SMALLEST
1. parvoviridea

2. polyomaviridae
3. papillomaviridae
4. adenoviridae
   - —————————
5. herpesviridae
6. poxviridae
   BIGGEST

1-4: naked
5-6: enveloped

Question 19

which DNA virus families are naked virions?

Answer 19

1. parvoviridea
2. polyomaviridae
3. papillomaviridae
4. adenoviridae

Question 20

which DNA virus families are enveloped virions?

Answer 20

1. herpesviridae

2. poxviridae

Question 21

what are the categories of RNA viruses?

Answer 21

1. positive RNA
2. double-stranded RNA segmented
3. negative RNA

Question 22

which virus families are positive RNA viruses?

Answer 22

1. picornaviridae
2. caliciviridae
3. hepeviridae
   - ————————-
4. flaviviridae
5. togaviridae
6. coronaviridae

1-3: naked
4-6: enveloped

Question 23

which virus family is a double-stranded RNA segmented virus?

Answer 23

reoviridae

it’s a naked virus!

Question 24

which virus families are negative RNA viruses?

Answer 24

MONONEGAVIRALES
1. rhabdoviridae

2. paramyxoviridae
3. filoviridae
4. bornaviridae

SEGMENTED
5. orthomyxoviridae

6. bunyaviridae
7. arenaviridae

**these are all enveloped virions!

Question 25

which virus families use reverse transcription?

Answer 25

1. hepadnaviridae 2. retroviridae they make DNA from RNA! they encode a reverse transcriptase retroviruses have an RNA genome and make DNA on the way in (first step after uncoating) hepadnaviruses have a DNA genome and make DNA on the way out (last step during assembly)

Question 26

what is the difference between positive RNA and negative RNA viruses?

Answer 26

positive strand RNA viruses are positive sense RNA so they match mRNA and can be directly translated into proteins negative strand RNA viruses are negative sense RNA so they have to make mRNA before they can make protein

Question 27

are most RNA viruses single or double stranded?

Answer 27

single there's only one double stranded: reoviridae

Question 28

virus classification table

Answer 28

slide 12

Question 29

which capsid symmetry do DNA viruses have?

Answer 29

DNA viruses have icosahedral symmetry except Poxviruses that have complex symmetry

Question 30

which capsid symmetry do positve stranded RNA viruses have?

Answer 30

positive stranded RNA viruses have icosahedral symmetry except coronaviruses which have helical symmetry 1. picornaviridae 2. caliciviridae 3. hepeviridae - ------------------------- 4. flaviviridae 5. togaviridae 6. coronaviridae 1-3: naked 4-6: enveloped

Question 31

which capsid symmetry to negative stranded RNA viruses have?

Answer 31

all negative stranded RNA viruses are enveloped and have helical symmetry!

Question 32

which type of capsid symmetry do reoviruses have?

Answer 32

they have multiple capsid shells they're naked virions!

Question 33

what capsid symmetry do the reverse transcriptase viruses have?

Answer 33

1. hepadnaviridae 2. retroviridae they both are enveloped and have icosahedral symmetry!

Question 34

what are the replication steps that have to happen for every virus?

Answer 34

1. adsorption/attachment 2. penetration 3. uncoating 4. synthesis 5. assembly 6. release penetration + uncoating = entry

Question 35

what happens during the attachment phase of virus replication?

Answer 35

the virus must bind to a receptor on a host cell the virion has some protein that can bind to the receptor on the host cell if the virion has an envelop, then there's proteins on the envelop that will bind to the host cell -- if it's a naked virus then proteins directly on the capsid will bind to the host cell VAP = viral attachment protein on virion

Question 36

how can we prevent virus attachment?

Answer 36

if we can stop the virus from binding to the cell then this would be great! we can make neutralizing antibodies or mAb that prevent the virus from binding to the receptor and stop it from the beginning

Question 37

what is VAP?

Answer 37

VAP = viral attachment protein on virion VAP is a capsid protein for naked viruses or it can be an envelope protein for enveloped viruses

Question 38

at what temperature will virion attachment occur?

Answer 38

4 °C

Question 39

what determines the tropism of a virion?

Answer 39

the binding of a VAP to the host cell receptor will define tropism of the virus if a certain cell or species doesn't have a receptor on their cell then the virus can't infect their cells! so maybe a virus can only infect liver cells but not neuron cells because they don't have the virus receptor

Question 40

what happens during the penetration phase of virus replication?

Answer 40

it's the process by which the virus is taken up into cells the actin cytoskeleton is involved in all endocytotic pathways! it's used to shuttle the virus around once it gets into the cell two general types: 1. occurs at cell surface = pH independent 2. occurs inside, after receptor-mediated endocytosis = pH dependent

Question 41

what happens during pH dependent penetration?

Answer 41

the virus enters the cell in an endosome and requires a specific pH trigger to allow for uncoating of the genome it will then use the pH in the endosome to start disassembling the virion as the cell moves along the actin cytoskeleton, the pH of the endosome will change as it matures which will help the virus with uncoating

Question 42

what happens during the uncoating phase of virus replication?

Answer 42

uncoating is the separation of the genome or internal nucleocapsids from the outer structural components of virions in some cases it is difficult to separate penetration from uncoating, both occur simultaneously you need to take the nucleocapsid apart so that you can translate the genome and make viral proteins

Question 43

what is the eclipse period?

Answer 43

it results from uncoating at this point you've disassembled the virion because you've removed the envelope and capsid if you tried to measure the virus in the cell right this moment, you wouldn't detect anything!! the person is still infected but there's no virus present because you've uncoated it and haven't yet replicated anything -- all the components are being made at this point before assembly

Question 44

what happens during the synthesis phase of virus replication?

Answer 44

synthesis phase starts after uncoating the virus genome directs the cell to synthesize "nonstructural" & "structural" proteins and more genomes the virus is trying to make viral proteins to copy more genomes and make proteins to synthesize new virions -- so the virus takes over the cell and and the cell is now only making viral proteins how the virus accomplishes this task depends on the "replication strategy of the virus"

Question 45

what's the difference between structural and nonstructural proteins?

Answer 45

structural proteins = proteins found in virion particles (ex. capsid) nonstructural proteins = proteins produced in infected cells but not found in virions nonstructural proteins just get used during replication but don't get packaged into the virion - usually they're enzymes that can replicate the virus but are not needed for infection

Question 46

what happens during the assembly and release phase of virus replication?

Answer 46

during assembly, the virions are formed by packaging the genomes with capsid proteins and if the virus is enveloped, wrapping the nucleocapsid in an envelope naked viruses accumulate in the cell and are released when the cell dies enveloped viruses acquire their envelope by budding through a membrane of the cell and are also released in the same step

Question 47

what is budding?

Answer 47

the process by which a virion acquires an envelope aka it only happens with enveloped virions! budding occurs at the plasma memebrane OR internally at the golgi, ER, nuclear membranes etc. and is specific to each virus there are matrix proteins that recruit the genome to a specific intracellular part of the plasma membrane -- the matrix proteins help the virus to associate the nucleocapsid with a specific site on the membrane that facilitates the budding process then at the end of the budding process, there are viral proteins involved to snip the connection with the cell so the virus is released

Question 48

what is a PFU?

Answer 48

PFU = plaque forming unit one virus can infect a single cell, spread and kill surrounding cells to cause a plaque (a clear area of dead cells) surrounded by live cells

Question 49

explain the hyperbolic growth of a virus?

Answer 49

immediately after infection, there's absorption, penetration, uncoating then there's the eclipse period where the cells are infected but we wouldn't find any virions during this time we're making viral proteins and synthesizing stuff and then all of a sudden you get a huge spike because eventually all the virions are released at once once the cell can't support the virus anymore

Question 50

what determines the viral replication strategy?

Answer 50

the viral genome!! the genome is the most important determinant; it's what determines what the virus has to do in the cell to replicate what the virus has to do to make mRNA to eventually makes proteins is different for RNA vs. DNA viruses

Question 51

what determines tropism of a virus?

Answer 51

VAP-receptor interaction

Question 52

what is a transient virus infection?

Answer 52

when the virus is cleared due to immune responses

Question 53

what is a persistent virus infection?

Answer 53

the virus isn't cleared by the immune response even if the immune response is fully active 1. chronic 2. latent 3. recurrent

Question 54

what is a chronic virus infection?

Answer 54

infectious virus is continuously present

Question 55

what is a latent virus infection?

Answer 55

the virus genome is present in cells but not infectious virions

Question 56

what is a recurrent virus infection?

Answer 56

a latent infection that reactivates and yields infectious virus before becoming latent (non-replicating) again

Question 57

what is a slow virus infection?

Answer 57

a chronic persistent infection with a prolonged incubation period of months to years and in which the disease symptoms progressively worsen to death

Question 58

how does the immune system clear viruses?

Answer 58

1. virus-specific antibodies 2. virus-specific T cells virus-specific antibodies “neutralize” or remove virus particles from blood or respiratory secretions, while virus-specific T cells eliminate virus infected cells, preventing persistence of the virus and of disease

Question 59

what do virus-specific antibodies do?

Answer 59

1. block receptor binding (neutralizing antibodies) 2. bind virus and prevent uncoating (entry blocking antibodies are neutralizing) 3. bind virus and remove coated virus particles via phagocytosis 4. may require complement to neutralize certain viruses

Question 60

what do virus-specific T cells do?

Answer 60

they kill virus-infected cells when they recognize virus antigens on cell membranes kill infected cells that present viral peptides using MHC I

Question 61

how do viruses cause disease?

Answer 61

1. they kill cells and result in organ failure 2. immune reaction to virus infection 3. virus infection induces autoimmune disease 4. congenital infection prevents or distorts organ development 5. virus infection provokes inflammatory state 6. virus infection induces an immunodeficient state

Question 62

what are some undifferentiated symptoms of viral infections?

Answer 62

fever myalgia malaise anorexia these symptoms occur after the host has responded immunologically and virus often is no longer present