Virus Replication Wk2 Flashcards

1
Q

How does virus enter through the skin?

A

Wounds, punctures
Animal/insect bite
Rabies

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2
Q

How does virus enter through eyes?

A

Aerosols, droplets, dust e.g. Herpes simplex virus

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3
Q

How does virus enter through respiratory tract

A

Inhalation e.g. Influenza

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4
Q

How does virus enter through intestinal tract

A

Ingestion, STD e.g. HPV, polio virus

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5
Q

Virus enters mucosal membranes by

A

Direct contact eg. HIV

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6
Q

Iatrogenic

A

Transmission via medical procedures
Shared needle eg. HIV

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7
Q

Vertical transmission

A

From parent to off spring
Breast milk =hiv

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8
Q

Viruses may remain at entry site

A

Skin, gut mucosa

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9
Q

Spread in localised tissues

A

e.g. Regional lymph nodes

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10
Q

Spread systemically to distant organs via blood, lymph neurons

A

Liver, spleen heart, nerves, brain

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11
Q

Attachment protein

A

Viruses bind to cells through their surface proteins

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12
Q

Receptor and co-receptor

A

Attachment protein binds via specific plasma membrane proteins

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13
Q

Cell tropism + host range

A

Cells susceptible to infection

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14
Q

Angiotensin converting enzyme 2 (ACE-2) SARS CoV-2

A

transmembrane protein
Involved in vasodilation

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15
Q

ACE2 is wide spread, respiratory, arterial, renal, cardiac cells

A

Wide cell tropism for virus

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16
Q

Binding of S1 subunit and ACE2 is the virus..

A

Attaching to cells

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17
Q

ACE2 receptor binding domain of spike protein research..

A

Target for drugs and vaccines

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18
Q

Influenza A virus attachment protein = haemagglutinin HA or H

A

Receptor = glycoprotein sugar side chains

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19
Q

Carbohydrate side chains which end with galactose + sialic acid only bind to..

A

Influenza A

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20
Q

Human influenza a bind to disaccharide in a …

A

-2,6 linked conformation
2nd carbon of sialic acid
6th carbon id galactose

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21
Q

Different isometric forms influence virus binding

A

Avian Influenza A viruses bind to the
disaccharide in an -2,3 linked conformation
2nd carbon of sialic acid
3rd carbon of galactose

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22
Q

Some enveloped viruses penetrate by fusion at the plasma membrane

A

HIV
measles
mumps

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23
Q

Many viruses trigger endocytosis, macropinocytosis or micropinocytosis

A

Virus attachment to the specific receptor
stimulates plasma membrane invagination
Virus is captured within a membrane
vesicle – capsid or genome must
escape to enter the cytoplasm
Ebola, rabies

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24
Q

Endocytosis, macropinocytosis & micropinocytosis vesicles
typically fuse with cell endosomes as the next step

A

Virus must escape from the endosome into the cytoplasm

25
Endosome escape mechanisms
require the action of a virus protein, typically activated by low pH (<6.0)
26
Enveloped viruses -
fusion of endosome membrane & virus envelope
27
Naked viruses -
lysis (complete rupture) of endosome membrane
28
Enveloped viruses -
permeabilization (localised rupture) of endosome membrane
29
Uncoating - Virus genome must be released into the cell
Plasma membrane, from endosome,into nucleus, through cell wall
30
Very small viruses may pass through a nuclear pore - capsid degrades / genome uncoats within nucleoplasm
Hepatitis B
31
Most viruses degrade capsid outside nuclear pore - only genome and few proteins enter nucleoplasm
Herpes simplex virus
32
Immediate early (IE) genes expression
- cellular RNA polymerase - promoters similar to cell promoters - transcribed as soon as genome uncoated
33
Delayed early (DE) genes
- cellular RNA polymerase - promoters have some similarity to cell promoters - transcribed after IE proteins made - Modify TFs and/or RNA polymerase
34
Genome replication
- cellular or viral polymerase - dependent on early proteins - Single or multiple origins
35
Late (L) genes
- cellular or viral RNA polymerase - promoters have unique - dependent on early proteins - mostly virion structural proteins
36
Human immunodeficiency virus is an exception
Genome is replicated first then integrated into chromosome - genome is transcribed from the integrated copy - all genes expressed from this integrated copy
37
Polio virus is also exception ( no early/ late genes)
Polio virus genome acts as mRNA - all genes are expressed together at the start (at low levels) - low levels of all virus proteins are synthesised - These are needed to transcribe / copy the RNA genome - all genes expressed again after genome replication
38
Virus genome replication
DNA or RNA synthesis = replication of virus genome (many copies made) = enzymes similar to cell DNA & RNA polymerases = variations of mechanism, dependent on virus genome - Baltimore classification
39
Assembly & exit of new viruses assembly = accumulation in cell of large numbers of new virus genomes & new structural proteins exit = genomes and proteins associate through specific nucleotide and amino acid sequence regions = formation of capsids and / or nucleocapsids
Exit = lysis, budding or exocytosis - usually cause the death of cell at some point
40
Baltimore classification
= genome structure, replication & transcription strategies
41
Class I dsDNA genome
Gene expression - may use cellular RNA polymerases or encode their own - mRNA transcribed from dsDNA (both invading and replicated copies) Genome replication - Viruses may use cell DNA polymerases or encode their own - varied mechanisms used by different viruses = theta (bidirectional) = rolling circle = strand displacement
42
Class II ssDNA genome +or- sense
Gene expression - may use cellular RNA polymerases or encode their own - mRNA transcribed from dsDNA intermediate formed during replication Genome replication - Viruses may use cell DNA polymerases or encode their own - strands are replicated sequentially - second (genome) strand made to high levels
43
Class III dsRNA genome
Gene expression - must encode unique RNA polymerase - mRNA transcribed from dsRNA intermediate formed during replication Genome replication - Relies on virus RNA polymerase Both strands are replicated simultaneously, in mechanisms similar to those seen for dsDNA replication NOTE: RNA synthesis = transcription
44
Class IV (+)ssRNA genome
Gene expression - must encode unique RNA polymerase - mRNA transcribed from (-)ssRNA formed during genome replication Genome replication Virus RNA polymerase (+) genome strand copied several times to make (-)strand intermediates Intermediate (-) strands copied many times to make new (+) genomes
45
Class V (-)ssRNA genome
Gene expression - must encode unique RNA polymerase - mRNA transcribed from (-)ssRNA genome and genome copies Genome replication Virus RNA polymerase (-) genome strand copied several times to make (+)strand intermediates (+)RNA intermediate strands copied many times to to make new (-) genomes
46
Class VI (+)ssRNA genome
Gene expression - uses cellular RNA polymerase - mRNA transcribed from dsDNA copy of genome once integrated into cell chromosome Genome replication Virus DNA polymerase = reverse transcriptase (+)RNA genome copied once to (-)strand DNA (-)strand DNA copied once to yield dsDNA dsDNA copy ligated into host cell chromosome (+)RNA genome transcribed repeatedly from integrated dsDNA by cellular RNA polymerase II
47
Class VII dsDNA genome
Gene expression - uses cellular RNA polymerase - mRNA transcribed from dsDNA genome Genome replication Cell RNA polymerase Virus DNA polymerase = reverse transcriptase Transcription (cell RNA polym,erase II) produces many genomic-length mRNAs (+ssRNA) Virus reverse transcriptase copies these to yield (-)ssDNA Same enzyme copies these DNA strands to produce new dsDNA genomes
48
Late gene expression results in
high concentrations of virus structural proteins
49
Icosahedral viruses –
empty capsids form first & genome molecule packaged
50
Helical viruses –
proteins typically assemble around the genome molecule
51
Assembly of helical viruses, tobacco mosaic virus
One gene encodes the capsid protein Multiple copies form a disk Disks assemble in pairs Genome associates with one disk Coat proteins change and disk becomes helix = locked washer More disks bind to each side Convert to helix as link Continue until whole genome enclosed
52
Assembly of icosahedral viruses (polio spontaneously)
One gene encodes the 4 capsid proteins, via cleavage of a polyprotein These bind together to form a hetero-trimer (protomer) – 5 protomers associate togther to form a pentamer 12 pentamers assemble to form an empty structure – a procapsid or provirion Genome is packaged into this immature provirion, usually through a modified pentamer
53
Assembly of icosahedral viruses (herpes scaffold)
Multiple genes encode several capsid proteins, and scaffold proteins Scaffold proteins allow assembly of a procapsid of structural proteins Scaffold proteins are subsequently digested, and virus genome enters the structure
54
Many enveloped viruses exit by budding at the plasma membrane (hiv)
1. Capsids migrate to cell membrane, virus glycoproteins accumulate in membrane 2. Capsid proteins interact with glycoproteins and pull membrane around capsid 3. Membrane “pinches off” when envelopment is complete = exit from cell = envelope acquisition
55
Some viruses bud at internal membranes
1. Capsids assembled in the nucleus can bud at the inner nuclear membrane 2. The new membrane is lost again by fusion with the outer nuclear membrane
56
Budding at ER and Golgi membranes triggers release by exocytosis
3. Capsids bud into the ER or 4. ER / Golgi vesicles bud out during Golgi – gain 1 membrane exocytosis – gain 2nd membrane - the 2nd membrane is lost by fusion with the plasma membrane
57
Exit of many non-enveloped viruses is achieved by cell lysis Polio
Cell membrane degrades & contents spill out, including newly-formed virions
58
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