EBV (Gamma herpesvirus)

Question 1

what cells do EBV infect?

Answer 1

B cells, epithelial cells

Question 2

what does EBV bind to enter B cells?

Answer 2

CR2 complement receptor (CD21)

Question 3

Difference between virions formed in B cells and in epithelial cells

Answer 3

• from B cells: better at infecting epithelial cells
• from epithelial cells: better at infecting B cells

Question 4

What binds to CR2 on B cell surface?

Answer 4

gp350

Question 5

Describe steps of viral entry into B cell in EBV

Answer 5

i) gp350 on EBV bind CR2 on B cells
ii) other contacts with viral glycoprotein, HLA II
–> entry thru endocytosis

Question 6

when does EBV circularize its genome?

Answer 6

after entering nucleus

Question 7

two types of viral proteins involved in latent EBV infection

Answer 7

i) EBNA (nuclear antigen)
ii) LMP (latent membrane protein)

Question 8

Small nuclear RNAs expressed in latent EBV infection

Answer 8

i) EBER1, 2
ii) miRNA

Question 9

function of EBER1, 2

Answer 9

help with malignant transformation by inhibiting apoptosis

Question 10

function of miRNA in latent EBV infection

Answer 10

bind to 3’ untranslated region of mRNA
–> silence translation

Question 11

Function of LMP1

Answer 11

i) help with growth transformation of B cells
ii) protect cells from apoptosis

Question 12

How does LMP1 perform its function?

Answer 12

mimic an activated tumor necrosis factor receptor (TNFR)
–> sitmulate growth pathway
–> stimulate NFkappaB + activate other cellular genes

Question 13

Function of EBNA1

Answer 13

i) initiate latent phase DNA replication
ii) segregate viral genome during cell division
iii) regulate transcription
iv) help with immortalization and survival of cells

Question 14

How does EBNA help with initiating latent-phase DNA replication?

Answer 14

recruit cellular replication to origin (e.g. MCM)

Question 15

How does EBNA1 segregate viral genome during cell division?

Answer 15

i) bind to FR sequence in EBV latent origin
ii) attach to mitotic chromosome thru interaction with EBP2

Question 16

How does EBNA regulate transcription?

Answer 16

i) bind to FR enhancer –> enhance transcription
ii) Repress transcription of Qp promoter

Question 17

What genes transcription does EBNA1 enhance when EBNA1 bind FR?

Answer 17

genes with LMP1, CP, Wp promoter

Question 18

How does EBNA1 help with cell immortalization/survival?

Answer 18

i) bind USP7 –> more p53 degrade
ii) induce degradation of PML protein –> loss of PML nuclear bodies

Question 19

Why does EBNA1 bind to USP7 increase degradation of p53?

Answer 19

USP7 used to stablize p53 by removing ubiquitination
–> disable p53 from binding to USP7

Question 20

What happens when more p53 is degraded thru action of EBNA1?

Answer 20

enable cel proliferation, prevent apoptosis