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MGY378 > Herpes simplex viruses > Flashcards

Herpes simplex viruses Flashcards

1
Q

Feature of genome in herpes virus

A

linear ds DNA
–> circularize upon cell infection

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2
Q

Three layers in herpes virion (from outer to inner)

A

i) envelope (with glycoprotein)
ii) tegument
iii) core

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3
Q

what is found in tegument of herpes virus?

A

viral, clelular proteins

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4
Q

Types of mammalian herpesviruses

A

alpha, beta, gamma herpesvirus

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5
Q

example of alpha herpesvirus

A

herpes simplex virus

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6
Q

example of beta herpesvirus

A

CMV

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7
Q

example of gamma herpesvirus

A

EBV

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8
Q

Difference between location of latent infection in herpes simplex and CMV

A

simplex: neurons
CMV: monocytes

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9
Q

Components of genome

A

i) Long (L)
ii) Short (S)

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10
Q

features of each gene component

A

i) unique sequence (U) flanked by inverted repeats
ii) L, S can be in any order

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11
Q

steps for HSV entry into cells

A

i) virus attach to cell surface receptor
ii) viral envelope fuse with plasma membrane
iii) capsid transported to nuclear pore
iv) DNA released into nucleus

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12
Q

what does virus bind to for entry?

A

gD: specific cell receptor
gH/gL: integrins

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13
Q

what helps with fusion of HSV with plasma membrane?

A

gB

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14
Q

How does the capside of HSV enter nucleus?

A

help of microtubules, transported to nuclear pore

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15
Q

What enters nucleus after capsid is transported to nuclear pore?

A

DNA, tegument proteins

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16
Q

Sequence of gene expression in HSV

A

i) alpha genes (immediate early)
ii) beta genes (early)
iii) gamma genes (Late)

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17
Q

what does gamma genes expresses?

A

structural proteins like capsid, envelope, tegument

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18
Q

What does beta gene express?

A

help in nucleic acid metabolism, DNA synthesis

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19
Q

when is beta genes in HSV expressed?

A

after alpha genes

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20
Q

what does alpha genes in HSV express?

A

regulatory proteins needed for gene expression

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21
Q

when does gamma genes express?

A

after DNA synthesis

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22
Q

What helps induce 1st viral gene expression in HSV?

A

VP16

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23
Q

How does VP16 induce viral gene expression?

A

bind to cellular protein (Oct1) that binds to alpha genes promoter

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24
Q

Function of ICP27

A

i) inhibit transcription, splicing of cellular genes
ii) role in mRNA transport
iii) activate expression of viral beta and gamma genes

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25
Q

What happens after VP16 bind to Oct1?

A

i) activate expression of alpha genes
-> also need binding to host transcription factor (HCF-1)

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26
Q

which viral proteins are expressed after help for VP16 in HSV?

A

4 IE proteins (ICP0, 4, 22, 27)

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27
Q

what is VP16?

A

tegument protein that is delivered to cell upon infection

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28
Q

Targets for ICP0 in HSV?

A

i) DNA repair proteins
ii) PML proteins

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29
Q

Function of ICP0 in HSV

A

i) promote lytic infection + needed to activate HSV from latent state
ii) degrade certain proteins like DNA repair ones and PML proteins

30
Q

What happens when HSV lack ICP0?

A

i) PML bodies form at incoming viral DNA
–> sequester viral DNA, proteins
–> prevent viral gene expression, DNA replication

31
Q

How does ICP27 in HSV alter splicing of cellular transcript?

A

i) inhibit activity of cellular splicing factors
ii) relocalize cellular REF (export proteins) to viral mRNA

32
Q

How does ICP27 help with mRNA transport?

A

binds to mRNA lacking introns and recruit REF (export protein) to viral mRNA
–> increased export of viral mRNA and opposite for cellular ones

33
Q

What cellular processes are inhibited in HSV infection?

A

i) host DNA synthesis (unable to enter S phase)
ii) glycosylation of host proteins
iii) host protein synthesis

34
Q

What reduces the protein synthesis of host in HSV infection?

A

i) ICP27
ii) vhs

35
Q

How is host protein synthesis reduced in HSV infection?

A

i) ICP recruit RNA pol II to viral replication site (unable to transcribe cell ones)
ii) ICP inhibit cellular mRNA export to cytoplasm by recruiting REF to viral mRNA
iii) mRNA degraded by vhs

36
Q

what does VHS stand for?

A

virion host shut-off

37
Q

function of vhs

A

destablize and degrades host and viral mRNA

38
Q

How does vhs degrade host and viral mRNA

A

i) vhs bind to host translation factors
–> bring it to polyribosome
ii) 5’ cap removed from mRNA –> then degraded

39
Q

What happens after vhs takes action?

A

i) remove pre-existing host mRNA – allow viral mRNA to take over translation pool
ii) destablize viral mRNA
–> transition from one class to another

40
Q

What controls the activity of vhs?

A

VP16 that is made late in infection
–> inhibit vhs activity

41
Q

What happens after VP16 binds to vhs?

A

packaged into virion

42
Q

How many origins of replication are found in HSV?

A

3

43
Q

Where are origins of replication found in HSV?

A

1 in L, 2 in S

44
Q

Viral proteins needed for replication of HSV DNA

A

i) UL9
ii) DNA pol
iii) ssDNA binding protein
iv) DNA pol processivity factor
v) complex with primase, DNa helicase activity

45
Q

Function of UL9 in HSV DNA replication

A

recognizes origin sequence + act as DNA helicase

46
Q

mechanism behind HSV DNA replication

A

theta structure
–> tho make linear dsDNA concatamer

47
Q

What happens before viral DNA into capsid?

A

scaffold destroyed by VP24

48
Q

Where does DNA packaging start for HSV?

A

packaging sequence

49
Q

describe steps in DNA packaging of HSV

A

i) capsid recognize complex formed on packaging sequence (a)
ii) DNA into capsid until capsid full and contact with another packaging sequence
iii) DNA cleaved with a sequence
–> asymmetric cleavage to make overhands

50
Q

Where is virion of HSV first eneloped?

A

nuclear membrane with viral proteins

51
Q

How does virions move from golgi to cell surface?

A

secretory vesicle

52
Q

Where do u get final envelope for virion of HSV?

A

golgi

53
Q

describe steps in viral egress of HSV

A

i) first enveloped in nuclear membrane
ii) enveloped virion enter ER
iii) lose envelope when exiting ER, gain another one in golgi
–> tegument proteins gained in cytoplasm
iv) Virions move from golgi to cell surface in secretory vesicles

54
Q

Where does virion lose its first envelope?

A

exiting ER

55
Q

Where does latent infection happen in HSV?

A

sensory neurons that innervate epihtelial cells

56
Q

transcript(s) expressed in latent HSV infection

A

latency associated transcript (LAT)

57
Q

Difference between lytic and latent infection of HSV

A

i) histone: lytic genes with histone for latent, no histone in lytic infection
ii) viral protein: only expressed in lytic cycle
iii) gene expression:
- LAT in latent
- alpha, beta, gamma genes

58
Q

Difference in histone modification for lytic and latent infection of HSV

A

lytic: no histone on promoter
latent: histone on lytic gene promoter (heterochromatin)

59
Q

Where is LAT expressed?

A

neuron-specific promoter with histone modifications allow TF access

60
Q

What protects LAT from heterochromatin modification?

A

insulator element

61
Q

function of LAT?

A

repress lytic gene expression in sensory neurons

62
Q

how does LAT repress lytic gene expression in HSV?

A

i) inhibit ICP0 expression by binding to its transcript
ii) miRNA encoded by LAT might also suppress

63
Q

When is HSV reactivated?

A

periodically

64
Q

How is reactivation induced experimentally?

A

i) express ICP0
ii) treat with histone deacetylase inhibitors

65
Q

What can promote reactivation of HSV?

A

i) physical/emotional stress
ii) hormonal change
iii) UV light

66
Q

Describe steps in reactivation of HSV

A

i) removed repression of chromatin –> VP16 expressed
ii) VP16 interact with HCF-1 in cytoplasm
–> bring into nucleus
iii) VP16/HCG-1 assemble on viral promoter (Oct 1 helps)
–> activate viral gene expression
iv) viral DNA replication
v) viral particles made and move to cells near initial infection site

67
Q

HSV with clinical attention

A

HSV-1, HSV-2

68
Q

Which HSV infection is more commonly infected?

A

HSV-1

69
Q

where does HSV-1 infection occur?

A

mostly mouth, sometimes genital areas

70
Q

Where does HSV-2 infection occur?

A

genitals

71
Q

complications in HSV infection

A

i) in newborns (damage eye or destroy parts of brain)
ii) to eyes (more of an issue for immunocompromised)

MGY378 (13 decks)

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