Viral Replication

Question 1

Different types of replication cycles

Answer 1

Virus infect and then a complete cell cycle occurs releasing progeny virus. Can either lyse the cell (cytolytic and productive) or be noncytolytic and productive usually with persistence of infection

Question 2

3 distinct phases in normal lytic cycle

Answer 2

Adsorption: virion count begins to drop as virus attaches to cells and initial repl stages begin
Eclipse: no virions as virus penetrates the cell, is uncoated and broken up to unmask the viral genome for viral component synthesis and replication to occur
Assembly and release: large virion number incr

Question 3

Adsorption and attachment process

Answer 3

Spec parts of virus capsid (capsomeres) or surf glycopros if enveloped recognise spec rec on cell surf

Question 4

What is a virus rec

Answer 4

A molecule (often a pp) on host cell surf that interacts with a component of the infecting virus in a spec way
A pre existing rec with integral role in normal host fx

Question 5

Rabies rec

Answer 5

Ach rec
Replicates in M cells
ach rec is next to neuromusc jctn
Rabies released and enter neuron via another rec. nucleic acid tracked up neuron to cell body and into brain

Question 6

Flu rec

Answer 6

Scialic acid
Haemaglutanin binds
Diff shape in diff species chicken straight human bent so cause some species specificity

Question 7

Influence of rec

Answer 7

Plays a role in disease type and pathogenesis

What cells are infected

Question 8

Penetration and uncoating: fusion

Answer 8

Only enveloped
Virus mem fuses with CM and necleic acid enters the cell directly
Regulated by spec domains on envelope glycopros
Mem and virus envelope have similar structure
Not all enveloped enter by direct fusion

Question 9

Penetration and uncoating: endocytosis

Answer 9

Felivers virus to endosomal vesicle with a lower pH than outside the cell
Lower pH (higher H+ conc) causes conformational shape change of virus pros req for entry and uncoating (enveloped induce fusion to exit endosome) (nonenveloped exit via conformational revealing hydrophobic fusion peptide (part of a virus capsid pro) that acts to form a pore in the mem)

Question 10

Fusion peptide action

Answer 10

Run of hydrophobic aas buried in 3D glycopro on virus. Virus bind rec, conformational change, fusion peptide freed, inserts into mem and brings mems together, splits the leaflets and fuses

Question 11

Why evolved to use endocytosis

Answer 11

Only healthy cells endocytose so virus only enters a cell that can replicate
Endosome trafficks to spec regions
Endosome pumps H+ in so pH down so conformational change induced

Question 12

Co receptors

Answer 12

Entry and uncoating often req a second or more cell surf molecules as well as the 1o rec (some viruses can have more than 1 1o rec)
If co rec not present then the infection wont proceed or will proceed very slowly

Question 13

Co rec eg HIV

Answer 13

Bind CD4 but not penetrate, need 2nd rec to induce conformational change for uptake

Question 14

Class 1 egs

Answer 14

Herpes
Adeno
Pox
Papo

Question 15

Class 1 replication method

Answer 15

dsDNA (linear or circular) genome
Most (except pox) repl in nucleus and are able to use host mech for transcription. Translation occurs in cytoplasm and then viral pps return to nucleus to finish repl process
Each family has own seq of events but Gen pattern of early pp synth, DNA repl, late pp synth
Only make what they need when they need it

Question 16

Why poxviridae not repl in nucleus

Answer 16

Very large and encode most of the enz req for repl. Repl in cytoplasm

Question 17

Early phase v late phase class 1 pp synth

Answer 17

Early: enz req for repl of viral DNA as rare to rely on host enz for this
Higher priority than struct pros (late synth)

Question 18

Class 2 egs

Answer 18

Parvo

Circo

Question 19

Class 2 req

Answer 19

Need late s or early G2 to repl so cell must be actively dividing and so they only kill cycling cells which influences the disease

Question 20

Class 2 repl process

Answer 20

ss DNA
Parvo eg: 2 grps repl autonomously and those that req a helper virus
Rely on cell DNA pol to make ss into ds
Parental DNA strand displaced and more compelmentary to new strand is synthed
Some steps dep on host cell fx only present in late S phase of cell division so autonomously dividing virus req actively dividng cells
mRNA transcribed from appropriate DNA strand and translated normally

Question 21

Class 3 egs

Answer 21

Reo/rotoviruses

Birna

Question 22

Class 3 repl process

Answer 22

dsRNA
Repl entirely in cytoplasm
Virus carries its own RNA dep RNA pol which transcribes -ve sense RNA strand to +ve sens mRNA (occurs within capsid)
mRNA extruded into cytoplasm and translated
dsRNA reformed by encapsidation of mRNA and synth -ve sense strand in new capsid

Question 23

Class 4 egs

Answer 23

Calici
Corona
Flavi
Picorna
Toga

Question 24

Class 4 repl process

Answer 24

+ve sense ssRNA
Genome same sense as mRNA and they code for all their repl fx themselves so genomic RNA infectious on its own
Picornaviridae is most studied and good eg

Question 25

Picornaviridae repl process (4)

Answer 25

Following cell entry Entire RNA length translated directly to make large pp pro, then cleaved proteolyticly in stages to yield struct (pps for capsid) and non struct (RNA pol and proteases) pros RNA pol then use genomic RNA as template for -ve complementary strand synth, which then fx as template for +ve strand synth req for further translation and assembly into progeny viruses

Question 26

Class 5 egs

Answer 26

``` Arena Bunya (seg) Filo Orthomyxo (seg) Rhabdo (nonseg) Paramyxo (nonseg) ```

Question 27

Class 5 repl process

Answer 27

-ve ssRNA All carry their own RNA dep RNA pol in virion to enable mRNA transcription Diff members have diff methods as some have segmented genomes and some don't (polycistronic) After entry, viral pol initiates mRNA transcription from genomic RNA (in cell cytoplasm except orthomyxo which does it in nucleus) Polycistronic genomes make monocistronic mRNAs and small no of polycistronic to be used as template for progeny -ve sense genome

Question 28

Class 6 egs

Answer 28

Lenti | Retroviruses

Question 29

Class 6 repl process

Answer 29

Genome +ve ssRNA RNA dep DNA pol (reverse transcriptase) make cDNA from ssRNA and then as it also has an RNase fx removes original ssRNA leaving single stranded DNA. Reverse transcriptase can also fx as a DNA pol so makes ssDNA into ds Dna then integrated into host DNA wear insertion becomes stable and is repl durin normal cell cycle. Normal RNA pol fron cell then transcr viral mRNA and viral genomic RNA from integrated DNA. Transl of mRNA makes pps to be processed further to produce pros for the virion

Question 30

Class 7 reversivirus repl process

Answer 30

Hep B DNA genome repl via RNA intermediate Genome partially ss and partially ds dsDNA to ssRNA to ssDNA to dsDNA

Question 31

Dna virus assembly location

Answer 31

Mainly in the nucleus except pox and irido

Question 32

RNA virus assembly location

Answer 32

Normally in cytoplasm

Question 33

Procaspid

Answer 33

Caspid assembly without nicleic acid (as it appears to occur spontaneously) so and empty procaspid

Question 34

Lipid cell envelope formation

Answer 34

Due to budding through lipid CM

Question 35

Assembly process

Answer 35

Formation of capsomeres from viral pps that aggregate to form a procaspid Nucleic acid inserted and may be proteolytic cleavage of some capsid pps

Question 36

Release process

Answer 36

Naked and the enveloped ones that bud through the internal mems may be released by cell lysis, sometimes released in a less destructive manner via normal cellular transport mechs Enveloped that bud through CM get released directly

Question 37

Direct release of enveloped virus

Answer 37

Viral glycopros expressed on cellular plasma mem Magrix pro binds to plasma men at base of viral glycopro acting as internal marker for ext viral pro presence Matrix pro has role in organising spatial array of glycopros and acts as site for nucleocaspid to bind Virus dev by invagination process of modified region of plasma mem causing release of complete virion

Question 38

Tropisms displayed by viruses

Answer 38

Species Tissue Cellular

Question 39

What determines virus tropism

Answer 39

All life cycle steps | Key: expression of viral rec by host cell and other cell factors altering susceptibility

Question 40

Parvovirus tropism eg

Answer 40

Repl Req cell fx only in late S or early G2 phases of cell cycle so can only repl in actively dividing cells

Question 41

How host cells may influence viral repl and vice versa

Answer 41

Action of transacting factors

Question 42

What may determine virus infection outcome

Answer 42

Differentiation state eg visna virus Infects macro and mono In mono growth and repl restricted so accum virus nucleic acid in cell with little viral pp and infectious virus synth When mature to macro or macro infected de novo the block to virus repl is removed so infection proceed as normal