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MIMM 324 > 4. Virus Entry > Flashcards

4. Virus Entry Flashcards

1
Q

is virus entry passive or active? why?

A

ACTIVE –> virus particles are too big to diffuse across the plasma membrane so they must be taken up by specific pathways

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2
Q

describe virus particles finding the ‘right’ cell (4 steps)

A
  1. adhere to cell surface via ELECTROSTATICS –> no specificity
  2. attach to specific receptor via glycosylated protein
  3. penetration
  4. transport and uncoating to release genome
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3
Q

describe receptors/attachment factors on the outside of the cell

A

proteins can be indirectly anchored by tethering to transmembrane proteins and some transmembrane proteins are glycosylated

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4
Q

describe what receptors/attachment factors look like on the inside of the cell

A

proteins can be indirectly anchored by tethering to transmembrane proteins and there are some lipid anchored proteins that don’t span the membrane

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5
Q

what specific type of molecule do viruses bind when they bind cell receptors? what is most common?

A

sugars –> sialic acid

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6
Q

what are attachment factors?

A

cell surface components involved in virion BINDING

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7
Q

what are receptors?

A

cell surface components involved in virion binding AND entry

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8
Q

what are some ways that receptors can trigger virion entry? (3)

A
  1. conformational changes
  2. cell signaling
  3. mediate endocytosis
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9
Q

are attachment factors and receptors only present in cellular membranes to allow virus binding?

A

NO!! they have specific cellular function

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10
Q

what is an example of an attachment factor?

A

sialic acid

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11
Q

viral receptors allow _______

A

viral receptors allow tropism

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12
Q

what are the 4 possibilities of viruses matching a receptor?

A
  1. different viruses can have the same receptor
  2. viruses in the same family may bind different receptors
  3. one virus may bind multiple receptors
  4. a virus may use different receptors on different cell types
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13
Q

how do naked viruses bind their receptors? (2 ways)

A
  1. capsid surface
  2. protrusions (spike proteins)
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14
Q

what do naked viruses do once they bind receptors? (2 possibilities)

A
  1. inject their genomes
  2. trigger endocytosis
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15
Q

how do enveloped viruses bind their receptors? an example?

A

using transmembrane glycoproteins (ex. sialic acid)

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16
Q

what are the 2 main virus entry pathways?

A
  1. endocytosis
  2. membrane fusion
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17
Q

which type of virus entry pathways do naked viruses use?

A

endocytosis only

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18
Q

which type of virus entry pathways do enveloped viruses use?

A

endocytosis and membrane fusion

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19
Q

2 examples of viruses that use endocytosis

A
  1. adenovirus
  2. poliovirus
20
Q

2 examples of viruses that use membrane fusion

A
  1. HIV (at plasma membrane)
  2. influenza (inside endosomes)
21
Q

what occurs during membrane fusion? what stimulates this process

A

2 membranes come together to become 1

stimulated by fusion proteins encoded by enveloped viruses

22
Q

what are the 4 steps for viral fusion at the plasma membrane for HIV?

A
  1. gp120 trimer binds to CD4 receptor and undergoes conformational change to allow binding to co-receptor CCR5
  2. gp41 (fusion peptide) inserts into cell membrane to form pre-hairpin intermediate
  3. gp41 HR2 folds back onto HR1 to form the six-helix bundle that brings the 2 membranes together
  4. a hemifusion stalk forms and becomes fusion pore
23
Q

what type of protein is gp41?

A

fusion protein encoded by virus

24
Q

how can gp41 insert into the cell membrane?

A

gp120 undergoes conformational changes so it binds to co-receptor which allows the hydrophobic part of gp41 to be exposed and it can then go to the cell membrane

25
Q

what type of secondary structure do HR2 and HR1 have?

A

alpha helix

26
Q

what changes in an endosome to trigger the fusion of some enveloped viruses?

A

low pH in the endosome

27
Q

what is the first part of viral entry for influenza?

A

endocytosis

28
Q

describe influenza entry in an endosome (4 steps)

A
  1. hemagglutinin protein (HA) binds to cell surface receptors that have sialic acid
  2. HA-sialic acid interactions promote viral endocytosis
  3. endosome acidifies
  4. acidification triggers a conformational change in HA that leads to membrane fusion
29
Q

what are the 6 steps of influenza membrane fusion?

A
  1. upon acidification, HA (fusion protein) is exposed and directed towards the target membrane by extending the coiled coil
  2. fusion proteins insert into the target membrane links the viral and target membranes
  3. if there are enough fusion proteins, a fusion pore can form
  4. a six-helix bundle forms
  5. hemifusion occurs as membranes are brought close together
  6. fusion occurs with the completion of the six-helix bundle
30
Q

how are class I fusion proteins aligned in the membrane?

A

perpendicular

31
Q

what type of secondary structure are class I fusion proteins made of?

A

mostly alpha-helix

32
Q

do class I fusion proteins form trimers or dimers?

A

trimers

33
Q

how are class II fusion proteins aligned in the membrane?

A

parallel to the membrane

34
Q

what type of secondary structure are class II fusion proteins made of?

A

mostly beta sheets

35
Q

do class II fusion proteins form trimers or dimers?

A

dimers

36
Q

why are class II fusion proteins hidden until they are needed? when do they stop ‘hiding’?

A

class II fusion proteins are hydrophobic so must be hidden until the right time bc don’t want it to attract the membrane –> conformational changes due to endosome acidification allow the fusion protein to stick into the cell membrane

37
Q

do class I and class II fusion proteins have similar mechanisms?

A

yes, even though the proteins are different

38
Q

what is the general mechanism for class I and II fusion proteins? 3 steps

A
  1. fusion protein hidden in native conformation
  2. conformational change allows insertion of fusion protein into the membrane
  3. protein/hairpin folds back to bring the membranes close together and initiate fusion
39
Q

describe membrane fusion of Dengue virus in endosomes (5 steps)

A
  1. dimer of E protein is anchored in the viral membrane
  2. upon acidification of endosome, the dimer dissociates and inserts the fusion loop into the endosomal membrane
  3. E protein trimerizes, allowing domain III to bind to a core trimer
  4. domain III flips to the side of the trimer, pulling the stem and transmembrane segments toward the endosomal membrane
  5. transmembrane segment is brought to the fusion loop, allowing hemi-fusion and opening of a fusion pore
40
Q

can naked viruses mediate membrane fusion?

A

NO!!!

41
Q

how do non-enveloped viruses get through cell membranes? ex. adenovirus and ex. poliovirus

A

non-enveloped viruses rely on the rupture of cell membranes
adenovirus –> ruptures endosome
poliovirus –> creates membrane channel/pore

42
Q

how do viral particles move within cells?

A

must be transported by vesicles or actin and microtubule cytoskeletons –> too big to move via diffusion

43
Q

when can viruses enter the nucleus? (2)

A
  1. during cell division when the nuclear membrane is broken down
  2. thru nuclear pore complex
44
Q

what is the nuclear pore complex?

A

1000s of nuclear localization signals that dock at the nuclear pore along the nuclear membrane

45
Q

how does the influenza virus get into the nucleus?

A

genome is segmented and segments diffuse thru the nuclear pore

46
Q

how do HSV-1 and adenovirus get into the nucleus?

A

virus docks at the nuclear pore and injects the viral genome into the nucleus

47
Q

how does parvovirus get into the nucleus?

A

disrupts the nuclear membrane and makes its own pore

MIMM 324 (37 decks)

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