Large dsDNA Viruses

Question 1

What is the typical large dsDNA family of viruses studied in class?

Answer 1

Herpesviridae

Question 2

Briefly describe the replication strategy of the herpesviridae

Answer 2

Attachment and entry by envelope fusion
Transport to nucleus and delivery of DNA
DNA circularizes in nucleus and replicates immediate early, early, and late proteins.
Late proteins are used for capsid assembly in nucleus
Capsid buds into AND out of ER from nucleus.
Capsid buds into Golgi and out of cell through membrane fusion taking Golgi membrane with it via exocytosis

Question 3

What does VZV cause? What kind of herpes is it?

Answer 3

Causes chicken pox (varicella) in children
Herpes zoster (shingles) in adults
Congenital varicella syndrome during pregnancy

Question 4

Describe chicken pox.

Answer 4

Is caused by the primary infection of VZV. Airborne and direct contact routes. Incubation period pre symptoms = 10-21 days. Remains latent in nerves.
HHV3

Question 5

Describe shingles

Answer 5

Is a reactivation of VZV that has been previously latent. Cuases painful rash and blitering of the skin.

Question 6

Describe Congenital varicella

Answer 6

Causes birth defects in babies and risks infant death. Only during pregnancy.

Question 7

How does shingles work?

Answer 7

Shingles results from a VZV reactivation from replication. Infection spreads from the ganglion to the skin in repeated cycles of productive infection which can cause rashes and be incredibly painful.

Question 8

Describe EBV. What kind of herpes is it?

Answer 8

Epstein Barr virus is HHV4. It causes Mononucleosis via the primary infection with EBV. Transmission via saliva.

Question 9

What kinds of cancers can EBV cause?

Answer 9

Burkitt’s lymphoma
Hodgkin lymphoma
Nanopharyngeal carcinoma

Question 10

Where does EBV remain latent?

Answer 10

CD19+ B cells

Question 11

Name some symptoms of mononucleosis.

Answer 11

EBV infection can cause fatigue, headache, photophobia, tonsil pain, lymph swelling, spleen enlargement, throat pain, cough, chills, fever, and aches as well as nausea.

Question 12

Describe the physical structure of EBV.

Answer 12

Envelope proteins gp350/220 binds to cell surface receptor CD21 on B cells (for uptake into endocytic vesicle) 
Envelope protein gp 42 binds to MHC class II (for fusion with endocytic vesicle and release into cytoplasm) 
Has linear genome which circularizes in host cell with terminal repeat sequences.

Question 13

What is a viral tegument?

Answer 13

A type of matrix protein assembly.

Question 14

How many genes does EBV code for?

Answer 14

86 genes

Question 15

Where does EBV infect? (Tissue tropism)

Answer 15

EBV infects several cell types including immune (B, T, NK) and somatic (epithelial and sm muscle).
Primary infection occurs in the tonsils

Question 16

What do EBV lytic genes do?
What kinds of lytic genes are there?
What do they do?

Answer 16

Control viral replication.
Immediate early, early, and late.
Immediate early are transactivators and enhace expression of later lytic genes.
Early block TAP Ag processing
Late makes capsid proteins

Question 17

What are the EBV lytic proteins?

Answer 17

Gp 350 and gp 110

Question 18

What two types of infection can EBV use? In what types of cells does this occur?

Answer 18

It switches between latent and lytic in B cells

Question 19

How does the immune system able to keep EBV in check?

Answer 19

It seeks out and destroys EBV+ B cells that are latent and present EBV antigens

Question 20

What does EBV promote in B cells?

Answer 20

Differentiation into long lived memory B cells

Question 21

How does EBV reactivate?

Answer 21

Because it creates long lived memory B cells these cells may reactivate in the germinal centers of the lymph nodes and this will lead to the production of virions in the lytic cycle.

Question 22

By what mechanism can EBV differentiate memory B cells?

Answer 22

LMP1 and LMP2 - Latent membrane proteins

Question 23

What are the functions of LMP1 and 2

Answer 23

LMP1 mimics CD40 signalling and promotes B cell proliferation. Inhibits apoptosis and DNA repair.
LMP2 mimics BcR signalling and promotes B cell survival

Question 24

What are EBNAs and LMPs and what do they do?

Answer 24

Epstein Barr Nuclear Antigens
Latent Membrane Proteins
The combination and density to which they are expressed on cells can cause or influence disease states. Most often lymphomas

Question 25

How do EBNAs and LMPs affect cellular transformation?

Answer 25

They lead to genomic instability often by the activation of ALT (alternative lengthening of telomeres) which leads to cancer.