Lecture 12 Flashcards

Macromolecular Synthesis

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1
Q

permissive cell

A

allow for productive virus replication

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2
Q

resistant cell

A

does not express the virus receptor

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3
Q

movement of large protein complexes will not occur by diffusion because

A

the cytoplasm is crowded

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4
Q

membrane fusion is regulated by

A

viral fusogens, (enveloped glycoproteins)

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5
Q

fusion is highly _____

A

regulated

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6
Q

what are the appropriate conditions for fusion

A
  • lower pH: plasma membrane (pH 7) or an endosomal membrane (pH 5-6)
  • binding to a second protein co-receptor (on plasma membrane or endosomal)
  • proteolytic cleavage (activates fusion protein)
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7
Q

fusion at the plasma membrane examples

A

sendai: viral attachment protein binds to receptor to stimulate a change and simulate a fusion peptide
HIV: viral attachment protein, interacts with receptor for HIV, binds to CCR and stimulates a change to push the fusion peptide in

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8
Q

fusion at an endosomal membrane

A
  • virions enter by endocytosis
  • acidification changes conformation of VAP (low pH)
  • reveals a hydrophobic fusion peptide
  • fusion peptide penetrates host membrane
  • further conformational change fuses membranes
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9
Q

what viruses are already on the “right side” of the membrane

A

enveloped viruses

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10
Q

how does a non-enveloped virus cross a membrane

A

makes a hole

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11
Q

how does a non-enveloped virus make a hole through the membrane

A

conformational changes in the capsid expose something hydrophobic: hydrophobic amino acid sequence, fatty acid

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12
Q

conformational changes can be due to

A

binding receptors, proteolysis, pH changes, etc

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13
Q

what promotes membrane reorganization

A

hydrophobic domains from viral fusogen

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14
Q

what is membrane reorganization

A

pore formation, membrane dissolution, usually use receptor-mediated endocytosis leading to endosomes

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15
Q

poliovirus (non-enveloped) makes what size holes

A

small

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16
Q

adenovirus (enveloped) makes what size hole

A

large

17
Q

poliovirus entry

A

-binds to its receptors
-conformational change reveals myristic acid
-myristic acid is ejected into membrane and disrupts the membrane
-allows hydrophobic amino acid residues to penetrate membrane
-creates a small pore in membrane
-the +ssRNA genome is injected directly into cytoplasm

18
Q

adenovirus entry

A

-initial binding to CAR by adenovirus fiber
-secondary binding to integrin
-acidification in endosome degrades capsid
-protein VI penetrates endosomal membrane
-membrane disruption allows remaining capsid to associate with microtubules and traffic nucleus

19
Q

viral polymerases

A

transcription and genome replication

20
Q

RNA viruses

A

-replicate in cytoplasm
-virus must use a viral polymerase
-viral RdRP generates both mRNA and new viral genomes
- +RNA virus must make a RdRP before any other transcription
- -RNA must package a RdRP in the virions

21
Q

DNA viruses

A

-replicate in the nucleus
-use Pol II to transcribe mRNA
-use host DNA-dependent DNA polymerases to replicate their genome
-drive cell cycle to S-phase
-replication is divided into early and late genome replication

22
Q

leaky scanning

A

-viral mRNA have start codons, can have poor Kozak consensus sequence
-scanning small ribosome subunit can sometimes miss these AUGs
-eg. Paramyxoviridae (measles)

23
Q

polyprotein synthesis

A

-entire viral genome is translated as a giant protein
-viral proteases self-cleave out and further process the genome
-eg. Picornaviridae (polio), Coronaviridae (SARS)

24
Q

why are virus particles built from sub-assemblies

A

ensures orderly formation and concentration dependent formation of viral particles

25
Q

how are virus particles built from sub-assemblies

A

formation of discrete intermediate structures
P1 cleaved to capsid proteins VP1, VP3, and VP0
these proteins assemble into pentamers which can form empty capsids
packaging of genome and cleavage of VP0 to VP2 and VP4 by a viral protease locks the capsid

26
Q

virus assembly occurs in

A

concentrated viral factories that are often visible by like microscopy

27
Q

viruses concentrate ______

A

proteins

28
Q

assembly and egress

A

acquiring an envelope
virus can acquire a membrane from cellular membranes, often the plasma membrane
viral glycoproteins accumulate on plasma membrane
recruit other viral proteins and the viral genome (matrix and nucleocapsid)
virion buds from surface

29
Q

virions can also acquire envelopes from

A

anywhere in the secretory system

30
Q

some virions require ______

A

maturation
APUTTGAR(M)

31
Q

maturation

A

proper maturation is required for virion infectivity in some viruses
e.g. HIV Gag polyprotein cleavage is prevented by protease inhibitors (Antivirals)