Lec 13 - Latent infections 2 Flashcards
which gene products are made and which are made less
- those promoting replication not made, or little bit
- those promoting latency are expressed
3 types of genomes in latent/persistent viruses
- non replicating genome in non divinding cell
- autonomously replicating genome in dividing cell
- integrated in host chromosome
wha is biggest viral family that uses latency
herpesviridae
what does epstein barr virus code for in the host cell
restricted number of transcripts
so a restricted number of proteins
so the host immune defences dont recognise it
alphaherpesvirus: role of envelope proteins
- recognsiing host cell
- bind to it
- getting in
- assist trafficking
alphaherpesviridae: tegument layer
function is unknown
but important for viral replication
what type of structure does alphaherpesviridae have
dsDNA
icosahedral
how many people sero positive for HSV1
80%
many wont experience reactivation and cold sores
where is the resovoir HSV
periperal nervous system
how does HSV end up infecting a sensory ganglion
- replicate in oral mucosal epithelial cells initially
- get into epi tissue
- get into sensory neurones and move to cell body via fast axonal transport
what happens once HSV gets into cell body
- cant be seen by immune system
- becomes latent
- if it gets reactivated, then can move back down peripheral neurone and reinfect mucosal epithelial cells
what could happen in HSV if immune system highly compromised
can move the other way from the cell body into the CNS
which would be fatal
what is the nucelosome-associated episome
virus is not integrated in host genome, but its genome exists in host cell nucleus
name of transcript that is expressed in HSV latency
latency associated transcript (LAT)
what does LAT transcript do
prevents expression of genes associated with lytic phase
and viral replication and assembly
during HSV acute infection: what is the trancriptional activator/tegument protein needed to encode immediate early genes
VP16
when does VP16 enter the cell
when the nucleocapsid enters the nucleus, it also enters
HSV1: how are genes usually transcribed
3 batches:
- immediate early = transc factors made etc
- early = proteins for replication
- late = assembly proteins
how is HSV infection of the neurons different
vp16 does not enter the nucleus = no transc of imm early genes
and only thing that is made is the LAT transcript
what key transcription factor does LAT transcript suppress
ICP0
what has been iimplicated as a possible reason for reactivation and why
-stress
-cortisol rises
- chromatin remodelling occurs
- may lead to release of the transcriptional silencing on the gene to code to VP16
varicella zoster: what complications might someone w chicken pox get
pneumonia
encephalitis
varicella zoster: where does it remain dormant
human ganglionic neurons
varicella zoster: when reactivates, what symptoms does shingles cause
painful vesicular skin eruption along sensory dermatomes
varicella zoster: where does it first replicate
macrophage
pneumocytes
(in lymph nodes and resp mucosa) = primary viremia
varicella zoster: secondary viremia
leaves blood vessels in T cells
infects epithelial tissue throughout body = rash, can be shed from lungs also
varicella zoster: during latency, how many genes are trancribed
5
varicella zoster: which of the genes transcribed in latency inhibit apoptosis
63
what family is epstein barr virus in
gammaherpesviridae
what % of people carrying EPV
85% of adults
where does EBV lie latent
non proliferating B lymphocytes
what cells initially get infected by EBV and how
subpharyngeal epithelial saliva
by saliva
what happens when a resting B cell is infected by EBV
replication of B cell is triggered
EBV: what are the 2 viral proteins expressed on surface of B cells
LMP-1 and LMP-2
which are targets for the immune system
EBV: how many survive and persist after the immune attack
1 in 100,000 only
and persist as non proliferating memory B cells
EBV: in the latent B cell, what viral protein is made in the nuclus
EBVNA-1
hidden from immune system
EBV: what protein is thought to initiate reactivation and how
Zta
by activating host erg1 gene = important for replication of EBV
measles: what is SSPE
subacute sclerosing panencephalitis
measles: when might SSPE happen
6-8 yrs after measles infection
measles: SSPE
cognitive decline
behavioural changes
seizures
gradual decline with no known treatment
measles: how might the virus enter neuronal cells in SSPE
fusion protein on measles virus gets mutated which allows it to recognise neuronal receptors which allows it access
