Chapter 11: Herpesviruses and other dsDNA viruses Flashcards
Virion
Typical "fried egg" appearance Large (120-200nm in diameter) Icosahedral capsid Enveloped ->spherical Genome: linear dsDNA Complex Icosahedral capsid Tegument Envelope Spikes
Hosts
Mammals, birds, cold-blooded animals
Infection
All can establish latent infection for a very long time
Asymptomatic or diseases of varying severity
Classification
> 100 viruses-> 3 subfamilies
Human herpesviruses
8 known in man Ubiquitous Most adults infected with most of them Transmitted in body fluid, droplets Initial infection -> latent infection -> reactivated
HSV 1 Structure
Capsid: several different protein, icosahedral, about 100 nm in diameter
Tegument: >15 different proteins
Envelope: Lipid bilayer with spikes
HSV 1 Genome
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
Adsorption
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
Entry, Uncoating, and transport
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
Virion host shutoff protein
- -> Degrade host mRNA and disaggregate polyribosomes
- Shutoff host protein synthesis
- Direct ribosomes and nt for viral synthesis
Transcription
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?
circular viral DNA
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
Translation
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
7 β gene products for DNA replication
- Ori-binding protein
- Helicase
- ssDNA-binding protein
- primase
- DNA polymerase
- 2 Polymerase processivity factors
Genome Replication
a. In nucleus
b. By viral DdDp and other β gene products
c. θ mode -> switch to σ mode -> concatemers
Assembly
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
Nucleocapsid
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
Exit
Vesicle and cell membrane fusion -> release virions
HSV normally destroys epithelial cells
Latent infection
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
Reactivation (induction) is caused by
Local stimuli
Systemic stimuli
Immunocompromised
VHS stands for
Virion Host Shutoff
