Herpes

Question 1

Herpes Simplex Virus basics

Answer 1

HSV1, HSV2

entry: epithelial, oral/genital

Primary: 1 - asymptomatic/sore throat

2- genital lesions, severe infection

latent: neurons
reactivation: genital lesions, cold sores

Question 2

Varicella Zoster Virus

Answer 2

entry: epithelial
primary: chicken pox
latent: neurons
reactivation: shingles/zoster

painful rash and post herpatic neuralgia

live attenuated vaccine for chicken pox, booster for shingles

Question 3

CMV basics

Answer 3

primary - usually asymptomatic, during pregnancy - birth defects

latent site: PBMC of myeloid lineage

reactivation - macrophage, bring virus around body, immune system usually controls but big problem if immuno suppressed

Question 4

HHV6, 7

Answer 4

primary: febrile illness for infants - roseola
latent: t cells, brain

reactivation?

Question 5

EBV basics

Answer 5

entry: epithelial cells
primary: mono, self limiting
latent: b cells
reactivation: if immunosuppressed, clonal B cell expansion, burkitt’s lymphoma or other cancers if immunosuppressed, correlates with geo regions

Question 6

Kaposi’s Sarcoma Associated Herpesvirus

Answer 6

entry - mucosal epithelia, sex, nonsex, saliva

primary - asymptomatic

latent?

reactivation - kaposi’s sarcoma - hard plaques when immunosuppressed, can kill!

Question 7

criteria for herpesvirus family

Answer 7

linear dsDNA

capsid

engelope

tegument

glycoproteins

Question 8

tegument

Answer 8

filled with proteins inside the envelope, outside the capsid

deliver stuff into target cell and capsid goes to nucleus

Question 9

herpes virus lifecycle

Answer 9

binding and entry

tegument proteins

IE (immediate early)

E (early) - DNA synthesis

L - late

envelopment and egress, DNA processing, capsid assembly

virions

Question 10

immediate early

Answer 10

first, synthesis of IE mRNAs and polypeptides

global regulators of viral gene expression, 1 immunomodulator

function of IE proteins REQUIRED for activation of E and L genes

Question 11

anti-sense phosphorothioate

Answer 11

antisense IE genes - target HCMV IE mRNAs

bind and RNase H cleaves mRNA:DNA hybrid

inhibit productive virus replication

Question 12

Early

Answer 12

synthesis of early mRNA and polypeptides - in nucleus

mostly involved in nt metabolism and viral DNA replication

DNA synthesis initates from viral genome, requires viral and host factors

viral replication machine assembles on genome to replicate DNA

Question 13

thymidine kinase

Answer 13

phoshorylates thymidine (and analogues - acyclovir)

cellular enzymes generate the active triP

acyclovir has greater affinity for viral tk than cellular tk, so active metabolite is only in infected cells

Question 14

acyclovir

Answer 14

direct incorporation into replicating DNA results in chains that are no longer substrates for further elongation

competitive inhibition of viral DNA pol

viral tk P acyclovir, cellular kinases activate

acyclovir only has affinity for viral tk

Question 15

Gangcyclovir

Answer 15

UL97 - protein kinase with cell and viral substrates

BCMV infected cells - not a nt kinase! but P gangcyclovir

important for viral growth

DNA chain terminator BUT has a lot of toxic side effects because very little specificity - can be incormporated into mnormal cell DNA that is replication

Question 16

Herpesvirus DNA replication

Answer 16

concatemer - rolling circle replication

single, extremely long DNA molecule with tandemly reiterated viral genomes

processing into unit length genomes late in the cycle

linked to assembly of mature viral particles - stuff capsids w DNA

Question 17

helicase-primase inhibitors

Answer 17

bind to unwind DNA -

composed of 3 proteins

enhance binding to prevent unwinding!

in cases of acyclovir resistance (HIV patients)

Question 18

Late

Answer 18

synthesis of late mRNA and polypeptides

structural capsid and tegument proteins

Question 19

scaffold

Answer 19

proteins self assemble into scaffold with protease domain and a small polyprotein

scaffold self digests itself and stuff DNA into capsid with rolling circle replication

Question 20

Foscarnet

Answer 20

targets DNA polymerase in early stage

Question 21

herpesvirus host response

Answer 21

generation of neutralizing antibodies against surface glycoproteins (protect against another primary infection)

cellular immunity neutralizes reactivation

immunocomp - can be severe!

Question 22

herpes virus evasion of immune system

Answer 22

clog proteasome

block TAP

rip MHC I out of ER and degrade

make MHCI decoys proteins

endocytosis of MHC I

also soe MHC II

Question 23

herpes and abs

Answer 23

grab ab so ag bing sites pointed away from grycoprotein target

Question 24

HSV latency

Answer 24

trigeminal ganglion, neuronal cell bodies

viral DNA is nuclear, circular, 20 copies/genome

chromatin silences expression!!

only viral products detected - miRs from LAT

respond to local stress/nutrients

Question 25

LAT

Answer 25

latency associated transcript

virus encodes a repressor of productve cycle genes

repressor encoded byLAT and expressed during latency

suppress apoptosis

Question 26

EBV latency

Answer 26

latent in B cells

B cells will divide (neurons don’t!)

critical to maintain genome so daughter cells get it

makes proteins during latency

1 copy of nuclear plasmid

Question 27

LMP-1

Answer 27

transmembrane protein - mimic for B cell CD4-

immortalizes B cell

to immortalize b cells and regulate their proliferation - const activates pways for normal b cell prolif

Question 28

Notch

Answer 28

deregulate notch through ebna-2 to immortalize b cells and regulate their proliferatin

Question 29

Zta (Zebra)

Answer 29

signal to mediate EBV reactivation - latent to productive cycle gene expression

viral site specific DNA binding protein/TF

acivates expression of productive cycle genes

results in DNA rep, virus production, death of host cell