Chapter 11: Herpesviruses and other dsDNA viruses

Question 1

Virion

Answer 1

Typical "fried egg" appearance
Large (120-200nm in diameter)
Icosahedral capsid
Enveloped ->spherical
Genome: linear dsDNA
Complex
Icosahedral capsid
Tegument
Envelope
Spikes

Question 2

Hosts

Answer 2

Mammals, birds, cold-blooded animals

Question 3

Infection

Answer 3

All can establish latent infection for a very long time

Asymptomatic or diseases of varying severity

Question 4

Classification

Answer 4

> 100 viruses-> 3 subfamilies

Question 5

Human herpesviruses

Answer 5

8 known in man
Ubiquitous
Most adults infected with most of them
Transmitted in body fluid, droplets
Initial infection -> latent infection -> reactivated

Question 6

HSV 1 Structure

Answer 6

Capsid: several different protein, icosahedral, about 100 nm in diameter
Tegument: >15 different proteins
Envelope: Lipid bilayer with spikes

Question 7

HSV 1 Genome

Answer 7

dsDNA, 152 kbp
Both strands used for coding
2 unique sequences: unique long region, unique short region
Repeat sequence
encode >74 proteins
2 copies of some genes in inverted repeats

Question 8

Adsorption

Answer 8

receptor mediated

a. Initial interaction
i. Receptor: heparan sulfate (proteocglycan)
ii. Antireceptor: gC (glycoprotein C) or gB
b. Further interaction
i. Receptor: 1 of several types of cell surface molecules
ii. Anti-receptor: gD

Question 9

Entry, Uncoating, and transport

Answer 9

a. Membrane fusion
b. Viral proteins involved in fusion: gB + gH/gL complex
c. Release nucleocapsid and tegument proteins in cytoplasm
e. Transport nucleocapsid to nuclear pore (“docking”) along microtubule
f. DNA injected into nucleus
g. DNA -> circularize
h. Some tegument proteins also enter nucleus

Question 10

Virion host shutoff protein

Answer 10

1. -> Degrade host mRNA and disaggregate polyribosomes
2. Shutoff host protein synthesis
3. Direct ribosomes and nt for viral synthesis

Question 11

Transcription

Answer 11

a. In nucleus
b. By host DdRp, but regulated by viral proteins
c. Circular viral DNA -> 3 classes of mRNAs distinguished by timing of expression
d. VP16 (as a transcription factor) activates IE genes
f. RNA processing by cellular machinery: capping and poly A tail
g. Most HSV-1 RNAs are not spliced – why not?

Question 12

circular viral DNA

Answer 12

i. α genes: immediate early genes expressed before DNA replication
ii. β genes: (delayed) early genes expressed before DNA replication
iii. γ genes: late genes expressed after genome replication

Question 13

Translation

Answer 13

a. In cytoplasm
b. α gene products: as transcription factors -> turn on β and γ genes
c. β gene products: -> for viral DNA replication (figure 11.9)
d. γ gene products: > 30 structural proteins
e. many α gene products -> block host responses to infection
f. Vhs protein -> shut off interferon synthesis
g. Spike glycoproteins
h. Translated on rough ER
i. -> glycosylated in Golgi

Question 14

7 β gene products for DNA replication

Answer 14

• Ori-binding protein
• Helicase
• ssDNA-binding protein
• primase
• DNA polymerase
• 2 Polymerase processivity factors

Question 15

Genome Replication

Answer 15

a. In nucleus
b. By viral DdDp and other β gene products
c. θ mode -> switch to σ mode -> concatemers

Question 16

Assembly

Answer 16

a. Capsid assembled in nucleus
b. Procapsid built on scaffolding proteins (removed later)
c. “Shell Stuffing”
d. Genome-length of DNA cut from a concatemer at a packaging signal
f. Nucleocapsid

Question 17

Nucleocapsid

Answer 17

i. Bud through inner nuclear membrane “patches” where tegument proteins accumulated
ii. Figure 11.12a
iii. Lose temporary envelope via fusion with outer nuclear membrane
iv. Released into cytoplasm
v. Acquire more tegument proteins
vi. Bud into a transport vesicle

Question 18

Exit

Answer 18

Vesicle and cell membrane fusion -> release virions

HSV normally destroys epithelial cells

Question 19

Latent infection

Answer 19

All herpesviruses can establish latent infection in their natural hosts
2 requirements:
1. the virus can evade host defense
2. the virus must not destroy host cell

Question 20

Reactivation (induction) is caused by

Answer 20

Local stimuli
Systemic stimuli
Immunocompromised

Question 21

VHS stands for

Answer 21

Virion Host Shutoff