6 Herpesviruses Flashcards
where are herpesviruses
widely disseminated in nature
how many herpes viruses are there
eight human herpesviruses have been isolated
what are the herpesviruses
- herpes simplex virus 1 and 2
- varicella zoster virus
- human cytomegalovirus
- Epstein-Barr virus
- human herpesviruses 6-8
herpesviruses genome
contain a linear, ds DNA genome
what encloses the capsid
capsid enclosed in viral tegument, lipid and glycoprotein envelope
Herpes simplex virus 1 (HIV-1) components
- core
- icosahedral capsid
- tegument
- envelope
Linear, dsDNA genome
Herpesvirus DNA - genome difference
- herpesvirus genomes vary greatly in size, base composition and structure
- genomes vary in length from 120kb to 230kb and contain different arrangements of unique and repeat sequences
what are HSV-1 genomes like
Segmented linear genomes Unique long (UL) and Unique short (US) covalently attached molecules
genes in unique long segment in HSV-1
> 62
genes in unique short segment in HSV-1
> 12
HSV-1 genomes UL and US segments
Both segments can be inverted
what effect does the inversion of UL and US segments cause
resulting in 4 different genome rearrangement possibilities
what are the 4 genome rearrangement possibilities
P, IL, IS or ILS
what are the sub divided herpesviruses
three sub-families on basis of differences in:
- host range and tissue tropism in vivo
- host cell range and growth characteristics in vitro
- site of latent infection
Herpesviridae classification
Beta, gamma and alpha
what do all herpesvirus encode
all encode many enzymes involved in metabolism (encode virtually all the genes that they need)
what occurs in nucleus
viral DNA synthesis and capsid assembly
what destroys the infected cell
release of progeny virus
what happens in cell entry
Herpes simplex expresses a range of surface proteins
Virus first has to be stabilised on the surface
Herpes virus glycoproteins interact with cell receptors
Will start a fusion with cell membrane and herpes will enter the cell
Endocytosed
low pH-dependent fusion
Micropinocytosis
pH-independent fusion
Expression of viral genes
Occurs in regulated cascade:
- immediate early genes: essential for co-ordinate regulation of other viral genes
- delayed early genes: encode proteins essential for viral DNA replication
- late genes: encode structural proteins
HSV-1 genome genes encode
Some genes encode early transcription factors ( genes)
Enhancer region
increase expression
where is the TAATGARAT sequence
upstream
in viral replication what is need
Enters as linear DNA
Organised into nucleosomes – tight and DNA condensed
Simplex genome enters – will be shut off unless HCF-1 opens it
HCF-1 host cell factor 1 open chromatin
what happens when virus first expressed
innate immune response acts quickly
how are cells killed
interaction between nucleofector that turns on all genes e.g. interferon, innate
lead to cell being killed
how is HSV-2 transmitted
sexual contact
how many adults are seropositive for HSV-2
10-30%
what is latency
establish latent infection infection in dorsal root ganglia of sensory nerves (stay at stable number in dorsal root ganglia – only one region of virus expressed – latent)
how can HSV-1 infect
Can enter through crack in e.g. nail
HSV-1 in eye effect
replicate in cornea (denrditic ulcer, then infect anterior chamber)
how can HSV-2 infect
Sexual organs
Mother giving birth with herpes simplex – high mortality rate for baby
which HSV causes brain bleeding
HSV-2
what is Alphaherpesvirus
VZV is endemic in most populations - chicken pox
Primary infection
how does Alphaherpesviruses infect
occur via the respiratory route
how many are infected by Alphaherpesviruses
At least 10% of population remain uninfected
what is HCMV
human cytomegalovirus
what are the herpesvirus 6 and 7
Betaherpesviruses
how prevalent is HCMV
Prevalence of HCMV in adult populations is 70%
what is HCMV a result of
- intrauterine infection
- perinatal infection
- intimate or sexual contact
- transfusion of whole blood, cellular products or solid organs
what is the seroprevalence of EBV
80-90%
where does EBV replicate
in epithelial cells of oro-pharynx
where does EBV establish latency
EBV establishes latent infection in dividing populations of B cells
what can primary infection with EBV cause
‘glandular fever’ syndrome
what is chronic infection associated with
associated with three important diseases:
- Burkitt’s lymphoma
- nasopharyngeal carcinoma
- other lymphomas
where is Burkitt’s lymphoma problematic
Burkitt’s lymphoma is endemic in the malaria belt of equatorial Africa
what is Burkitt’s lymphoma associated with
100% of endemic BL is associated with EBV infection
what causes Burkitt’s lymphoma
arises in B cells expressing type 1 latency
how does Nasopharyngeal carcinoma arise
Arises from epithelial cells expressing ‘type II’ EBV latency genes
what does Nasopharyngeal carcinoma require
additional environmental and genetic co-factors
