#14 herpes viruses Flashcards
what type of virus is herpesviridae?
persistant virus - it is latent
- will have spurts of no detectable virus
- will reactivate and produce viral shedding
- sometimes can be shed without any symptoms
what are ways viruses can passively evade the host defence?
- infect non replicating cells
- infect cells that dont express MHC i.e. Neurons
- target sanctuary sites i.e. eye
- target immune cells
-spread by cell fusion: syncytia
be transported via free passage through the skin or mucosal layer i.e. organ transplant or needle
what are active evasion mechanisms used by viruses
- limiting viral gene expression
- non-cytopathic infection
- block immune defences
- block apoptosis
- generate immunosuppressive and anergic epitopes
what is a characteristic of latent infection
- having long periods of low or undetectable virus or disease
herpesviridae - what type of genome enveloped? how big is genome cytopathic?
dsDNA linear enveloped large genome 150kB cytopathic infection latent infection
when will herpesviridae reactivate
after immunosuppression or stress
what viruses are in alphaherpesviruses
where do they infect?
- HSV1 and HSV1
- Varciella Zoster virus VZV
- they infect neurons
what viruses are in betaherpesviruses
where do they infect?
Cytomegalovirus (CMV)
Human herpesvirus 6 (HHV-6)
Roseola infantum (red cheeks)
they infect monocytes and on secretory tissue
what viruses are in gammaherpesviruses
where do they infect?
Epstein Barr virus EBV
Kaposi sarcoma virus HHV-8
they infect lymphocytes
b-cells for EBV
are any genes made from herpesviruses during latency?
minimal gene expression during latency - however LATS are made during latency
i.e. EBNA-1 to 6 for EBV
when are the early and late genes for herpesviridae made in relation to viral DNA replication
early genes including regulatory genes are made before the viral DNA replication
late genes include the capsid and envelope which are only made after viral DNA replication
name an early gene produced for HSV
HSV thymidine kinase
how does the viral genome of herpesviridae persist in the cell
- it exists as a circular episome
- present in the nucleus
- ## there are two forms of the episome - replicating and non-replicating (latent genome)
explain EBV replication during latent stage
- EBV infects B-cells
- every time the B-cell divides the latent EBV will replicate too
- EBV Ori-P will be used to replicate the episome in latent infection
EBNA-1 will bind to Ori-P - the circular genome will be replicated
explain EBV replication during lytic stage
- promotor used will be Ori-Lyt
- replication will occur via rolling circle
- the linear DNA will be replicated
- new virus particles are made
how does EBV seperate the lytic and latent replication of virus?
it uses two promoters
- Ori-P for latent infection
- Ori-Lyt for lytic infection
what does HSV in the CNS cause
herpes simplex encephalitis
how is herpes simplex encephalitis diagnosed
PCR of CSF fluid
how does primary infection of HSV work
- virus replicates on skin
- gains access to sensory nerves
- travels via retrograde transport to nerve body
- latent genomes in nerve (T-cells keep it in check)
- virus usually doesnt transfer on to the brain
how does HSV re-occur?
- travels via axonal transport
- cause cold sores on same spot it initially infected
what is expressed in a latent infected cell of hsv?
- genome is present
- no structural genes
- some LAT mRNA
(no LAT proteins)
what family is varciella zoster virus
herpesviridae
what does VZV cause
- initial infection is chicken pox
- can resurface as Zoster (shingles)
explain the infection process of VZV
and how it goes latent
- infection of conjunctiva or mucosa of RT
- viral replication in regional LNs
- primary viremia
- further replication in liver and spleen
- secondary viremia
- infection of skin causing vesicular rash (chickenpox)
- it will gain access to the sensory nerves and lay dormant in the nerves - can spread throughout the ganglion
- will resurface as shingles across a whole dermatome (commonly associated with immune deficit)
how do you treat VZV
antiviral chemotherapy
or
passive immunisation with Zoster immunoglobulin
what type of vaccine is the chickenpox vaccine
live attenuated
what type of virus is EBV
-herpesviridae
what does EBV cause
glandular fever
infectious mononucleosis
how is ebv aquired
direct contact of oropharynx with infected saliva
what is a characteristic sign of EBV infection
swollen lymph nodes
where is productive infection of EBV made?
where is latent infection?
in the nasopharynx and salivary glands - virus is produced here
latent infection is in B-cells - virus does not replicate here it is just the site of latency
what percentage of people are infected with EBV
90%
explain the process of EBV infection
- Primary site infection is the oropharyngeal cavity (URT)
- Initial infection is lytic in the epithelial cells - there is expression of full complement of viral genes
- It then Spreads to B cells as they come to defend
- generates widespread immune response (e.g. CTL response) – results in swelling of the lymph nodes.
B-cells become the reservoir for latent infection
- Episome is maintained by Ori-P and EBNA-1 viral protein in b-cells! (non-productive replication)
are there any genes expressed in latent EBV infection? what are they
limited no. of genes expressed
EBNA 1 to 6 are expressed
LMP 1 & 2
what is the job of EBNA1 in EBV infection
- used in latent stage in b-cells
- needed to replicate the episome in non-lytic phase
- will bind to the Ori-P region and drive replication in dividing b-cells
needed for viral replication in latency
what are the 3 types of EBV infection with in b-cells and what diseases to they result in
- Type I: has all 9 latent Antigens, will result in lymphoproliferative disease
- Type II: has 3 latent antigens, will result in Hodgkin’s lymphoma
- Type III: only the EBNA-1 antigen, results in Burkitt’s
tumorogenesis is associated with what virus in herpesviridae?
EBV
what family in CMV
herpesviridae
who is at particular risk of CMV?
newborn babies - it is the leading cause of still birth
CMV infection can cause deafness, blindness, microencephaly
also a major cause of death in bone marrow transplant patients
what can reactivate CMV in adults?
immunosuppression i.e. AIDS
