Herpes Virus Flashcards
What type of viruses are herpesviruses?
Double stranded DNA viruses
How many herpes viruses cause disease in humans
8
Give 4 structural features of herpes virus
- Core containing the large ds genome surrounded by a proteinaceous core
- The complex icosahedral capsid surrounds the core
- Outside the capsid is the tegument, a protein-filled region
- On the outside of the particle is the envelope which contains numerous glycoproteins
What are the two distinct life cycles?
- Lytic which produces infectious virions causing cell destruction and allowing the virus to spread
- Latent infection allows the ability to persist indefinitely
What are the 8 subfamilies of herpesvirus?
Gammaherpesvirinae
Betaherpesvirinae
Alphaherpesvirinae
What are the three groups in alphaherpesvidinae?
HSV1
HSV2
VZV
What are the three groups in betaherpesvirinae?
HHV7
HHV6
CMv
What are the two groups in gammaherpesvirinae
KHSV
EBV
What is the result of HSV1/2?
1 is common cold sore and 2 is genital herpes
Which group of herpes viruses are the largest?
Beta, associated with Alzheimer’s lesions
Which group have oncogenic potential?
Gamma
Which sub-family has has the most restricted host range and which has the most variable host range and why?
Most - gamma, replicate in lymphoblasoid cells, lytic in epithelial cells. Latent in T or B cells
Least - alpha, spread rapidly, efficient cell destruction. Latent infection in sensory ganglia
How many gene products does HSV code for?
80
How are the two segments in the genome linked?
Covalently, flanked by inverted repeats
What do the inverted repeats allow?
Rearrangements of the unique regions, genomes exist as a mixture of 4 isomers.
How many genes are pathogenic?
40
What does virus entry require?
- gB and gC glycoproteins bind to cell surface proteoglycans
- Attachment is then stabilised by gD binding to herpesvirus entry mediators, Hve A, B and C.
- pH-independent fusion of the viral envelope with the cell plasma membrane
gB, gD, gH and gL are involved.
How are viral protein groups expressed?
Temporal cascade fashion. IE switches on the expression of viral genes which include enzymes required for DNA metabolism and replication so structural genes can form the virus particle
How is IE expression initiated?
Recruitment of cellular factors to IE promoters enhanced by the tegument protein VP16 or aTIF
What does VP16 interact with?
Oct-1, HCF, TFIIB and TFIID
What do IE genes do?
Regulate E and L gene expression as well as providing cellular environment conductive to viral synthesis
What is ICP0?
Promiscuous transactivator of all classes of HSV genes, interacts with cellular factors allowing transactivation of early promoters. Disrupts cellular ND10 (sites of cellular transcription) providing an environment for conducive viral synthesis. Prepares the cell for replication
What is ICP4?
Essential for transactivating all early and late genes, interacts with cellular factors, allowing recruitment to early promoter
What is ICP22?
Enhances expression of ICP0
What is ICP27?
Transactivates late genes, acts at a post transcriptional level. Stabilise viral mRNA and transports it from nucleus enhancing translation
What is ICP47?
interferes with host immune response: affecting MHC class I presentation
What is ND10?
Promyelocytic leukemia nuclear bodies, discrete nuclear foci that contain several cellular proteins involved in diverse processes such as transcription, chromatin structure, DNA repair and apoptosis
Name 7 genes which are essential for virus genome replication
- UL9 origin binding protein
- ICP8 ss DNA binding protein
- UL5/UL8/UL52 helicase/primase complex
- UL30/UL42 DNA polymerase
Describe herpes virus genome replication
- UL9 binds to one of the 3 replication sites and the genome circularises
- In conjugation with ICP8 the DNA bends forming a stem-loop and unwinding the DNA
- Helicase-primase binds the ssDNA and synthesises RNA primers
- Viral polymerases bind RNA primers and start the synthesis of DNA
What form is the genome replicated in?
A rolling circile intermediate forms Concatemeric strands
How are viruses assembled?
Procapsids are formed first around the scaffold proteins. These are digested away so the capsid can incorporate the DNA through a portal. The terminase proteins UL15, UL28 and UL33 act as an ATP-dependent pump that drives the DNA into the procapsid and cuts the concatemeric DNA
How does the virus exit the nucleus?
- Budding at the inner nuclear membrane leads to presence of enveloped primary virions in the perinuclear cleft
- Fusion of the primary envelope with outer nuclear membrane
- Pass through the outer membrane where the primary envelope membrane is lost.
- Associates with tegument proteins and bud into golgi-derived exocytotic vesicles
How do viruses access the neurone?
Through the axon-terminal, removes the tegument layer
What is the role of LAT?
Keep the genome silent and avoid host immune surveillance, prevent apoptosis. Processed to expressed 4 miRNAs which prevent the expression of lytic regulatory proteins (ICP0)
How does a latent episome reactivate?
Reorganise its chromatin and accumulate HCF-1 and VP16
What is acyclovir?
Antiviral which specifically targets the herpes DNA replication mechanism
How does acylovir interrupt DNA replication
Thymidine kinase phosphorylates acyclovir. It is incorporated into the DNA and prevents chain elongation.
What are helicase-primase inhibitors?
Prevents progression through helicase of catalytic cycles
