k? (L19) Flashcards
Herpesvirus particle
Based on morphology, herpes viruses are all alike. But this picture shows specific characteristics that tell us it’s a herpes virus
The core - symmetrical icosahedron
Classic viral capsid structure surrounded by a thick layer (tegument) around the core
Tegument is a key defining feature - made up of virus coded proteins and is important to life cycle
ALSO IMAGE OF STRUCTURE IN L19 S2
envelope and its glycoproteins
genome size
coding capacity
Envelope has a variety of virus coding glycoproteins on it
(influenza has 2 major glycoproteins on envelope, but this herpes virus has at least 6 glycoproteins)
They are large and complicated (more complicated than smaller rna viruses)
Symmetry isnt perfect - even if it is icosahedral, one of the vertices in the portal vertex is very different in structure and has a very particular function in the life cycle (it’s how the genome gets in and out of the nucleus)
Genome size is massive (125 to 230 000 nucleotides) compared to the flu genome (14 000 nucleotides). Could make 100 proteins.
Some make up this complex particle, some are involved in replicating the genome
They encode things that modulate the interactions with the host - change the way the host perceives the infection (deal with innate immunity) , and allow the virus to have a complex multiphase life cycle
Across the herpes virus, there is a big spectrum in their coding capacity
In the smallest end, there is almost ½ the genome size of the largest end
Amongst this very large family of viruses, there is a lot of variation in how much coding capacity they have, and what they do to interact / modify the host they invade
family of herpes virus
TABLE IN L19 S4
The alphaherpesvirus subfamily
herpes simplex 1 & 2; varicella-zoster
in vitro:
HSV grows easily to high titres in many cell types
VZV is more restricted, and is highly cell associated (less easy to study)
in vivo:
Establish life-long latency in cells of the nervous system
Episodes of productive virus infection in epithelial cells
In cell culture, we can study the virus because they replicate very readily, and when it is placed in the host cell it will destroy it and release hundreds of copies → cytopathic infection
Varicella is difficult in cell culture, doesn’t kill the cell and quickly and easily, difficult to study BUT when taken in the host, they BOTH have similar biologies
They illustrate 2 distinct types of interactions → in epithelial cells they produce productive infections BUT in neuronal cells they establish life long latency without killing the cell
Herpes Simplex Virus Infection
- Infection of epithelium and replication
- Infection of sensory nerve endings and transport to cell body
- Establishment of latency
- Reactivation
MORE DETAILS IN L19 S6
cold sores
Cold sores - simplex type 1 infection
They do reoccur in the same area - shows the infection re-travelling back to the same place to infect the skin
Simplex type 2 - same in genital tracts
Varicella zoster - same
VARICELLA PHASES:
First phase - chicken pox
Each blister has a large amount of these viral particles
All nerve endings that are innovating the whole body, are becoming infected, and the virus is going back down to lie dormant in the ganglia of the spine → so means that any part of the body in vulnerable in the future to the reactivation of varicella zoster
Zoster - shingles - occurs when reactivation establishes productive infection on that area which is innovated by the same ganglion (so reactivation of many nerves)
But vis a vis reactivation dont occur as often as HSV (they are much more painful and serious)
When you have chicken pox, you are very susceptible to shingles
HSV1 genome organization
Most genes encoded in the unique L and S portions
Some genes within RL or Rs and hence two copies per virion (diploid)
Genome - simplex type 1 is at 150 bp
Chunks of the genome are repeated
green/pink - different types of repeated sequences (usually means that something is functionally significant)
Green - long and are coding sequences
Virus is partially diploid for some genes
recombination
Genome can have different architectures but still be the same virus - this works via recombination
2 copies of the same sequence are aligned side by side
The L sequence of dna is now inverted
Same thing can happen around the short segment
DIAGRAM IN L19 S9
possible isomers after recombination
4 possible isomers: standard
L inverted
S inverted
both inverted
herpes virus LIFE CYCLE
- attachment
- entry into host cell
- fusion event
- herpes simplex virus attachment
multiple interactions between viral surface glycoproteins and host cell receptors
gB and/or gC are the attachment proteins
binds heparan sulphate
HSV virion attaches to heparan sulphate proteoglycan on filopodia. This requires glycoproteins gB and/or gC.
virions then migrate (‘surf’) towards the cell body
Lipid envelope has many glycoproteins - gives it the possibility to interact with diff cell surface molecules on diff target cells
Glycoprotein B and C are the main attachment proteins (simply attaching to host cell isn’t the end of entry)
First attachment enriches virus on surface of cell - non specific interaction that the virus can exploit
Interaction with those proteins will allow other proteins to get involved for the virus to enter the host cell
- entry into host cell
Entry takes one of two possible modes:
1) Entry by fusion at the plasma membrane.
This requires additional receptors recognised by gD, gH and gL.
gD binds to Ig-family molecules: nectins
2) Entry by endocytosis followed by fusion at the vesicle membrane.
This requires additional receptors recognised by gD, gH and gL.
gD binds to Ig-family molecules: nectins
- fusion event
After HSV Entry
the fusion event delivers the nucleocapsid to the cytoplasm.
the nucleocapsid moves through the cytoplasm and interacts with nuclear pore to deliver the dsDNA genome to nucleus.
first phase of the infectious cycle
HSV1 Gene Expression (and protein names)
protein names:
ICPx: Infected Cell Proteins in decreasing size order
VPx: Virion proteins in arbitrary order
VmwXX: Virion proteins by size (in kDa)
ULx or USx: Arbitrary designation by open reading frame
IExx: Immediate Early protein of size xx (in kDa)
transcription is by host RNApol II in the nucleus
gene expression is in several distinct, temporally regulated phases
activation of IE genes by VP16
VP16 forms complex with host cell factor (HCF) which targets it to the nucleus where it binds a target sequence
GyATGnTAATGArATT (y=C/T; r=G/A)
Binding of VP16/HCF to ‘GArAT’ requires binding of host transcription factor Oct1 to ‘ATGnTAAT’
