Micro-L5- Herpes and Papilloma

describe what group herpes and papillomaviruses are: and where it replicates, genome type etc. what does it have/not have what

• group I- dsDNA

• replicates in the nucleus(except poxviruses) using host machinery

• papilloma- uses host DNA polymerase and encode regulatory proteins to recruit host replication- CIRCULAR GENOME in REPLICATION

• herpes- l- uses host RNA polymerase for TRANSCRIPTION. makes own DNA polymerase- LINEAR GENOME

what are the hallmarks of herpes viruses? what are the phases?

it is persistent

1. latency- with minimal gene expression, no virion production and genome is maintained in a host cell

2. lytic phase- full gene expresion, DNA replication, virion assembly and cell damage

describe the herpes virus structure

• smaller than smallpox but big virus

• linear dsRNA and has 70-200 genes

• has multiple origins of replication

• nucleocapsid: icosahedral protein capsid

• tegument layer: has a protein rich layer between the capsid and envelope- has viral proteins needed upon entry: transcription activators, DNA replication proteins and immune evasion proteins

• has a lipid enevleope- from host membranes and viral glycoproteins for attachment

descrie the early steps of HSV replication- how it binds and enters

1. virus binds to host cell via non specific receptors- interacting with the proteoglycans in the EM

2. fusion of the viral envelope with cell membrane

3. viral core nucleic acids are released into the cytoplasm

4. viral core is transported via host microtubules to the nucleus through the nuclear pore

5. viral genome released into the nucleus

6. linear genome becomes circularised

describe the HSV transcription and gene expression and how it is controlled- what genes ae transcribed, what it needs

1. immediate early alpha genes

• viral proteins interact with host transcription machinery by using HOST RNA polymerase II

• controls transcription, counter host defences and block immune response

2. early beta genes

• immediate early proteins act as TF

• early mRNA is exported to the cytoplasm for translation

• works in DNA replication and DNA synthesis

3. late genes

• activates after viral DNA replication begins

• encodes structural proteins- capsid proteins and glycoproteins

describe how HSV genome replicates

• HSV genome circularises in the nucleus

• rolling circle replication model

• uses its own DNA dependent DNA polymerase to replicate viral genome- produces concatemeric DNA molecules

• viral enzymes cuts the concatemers into individual linear gene lengths

• genome length DNA is packaged into new virus particles

how does the HSV gene assemble? what is required?

• capsid assembly occurs in the nucleus around the viral genome

• needs scaffolding proteins(like poxvirus) and forms large protein complex shells for the capsid. participate in nucleic acid construction but not viral fusion to make mature virion

• chaperone proteins assist in accurate capsid assembly

• these scaffolding proteins are proteolytically cleaved as the capsid matures and leaves space for viral DNA to be packaged inside

describe herpes lytic transcription

• incoming viral DNA enters the nucleus and becomes ciruclaised

• gene expression occurs in 3 regulated phases: immediate, early and late

• immediate: viral gene transcription and counter host defence, early involved in DNA replication and late is activated AFTER viral genome replication begins

describe how HSV egresses? compare this to the poxvirus

• poxvirus forms an intracellular envelope particles and double membrane- and fuses

• through a complex, multi-stage mechanism involving nuclear budding, de-envelopment, and cytoplasmic re-envelopment.

• buds through the inner nuclear membrane as its too large- gains a tempoerary membrane

• then fuses with the outer membrane- loses this membrane

• capsid into vesicles from golgi- get another envelope. In the cytoplasm, the capsid acquires a tegument (protein layer) and buds into Golgi-derived vesicles or endosomes that contain viral envelope proteins, creating the final, mature infectious particle.

• acquires its final envelope and tegument from the Golgi apparatus, and exits the cell via exocytosis

how does HSV transmission occur?

cell-to-cell transmission

1. extracellular spread- virus particles are released from the infected cell and travel through the extracellular environment to infect another cell. for HOST-TO-HOST transmission

2. direct cell-to-cell- virus spreads directly between neighbouring cells and doesn’t need release into the extracellular environment

why does HSV go latent? and what does this mean? why does this allow?

• goes latent- means limiting gene expression and allows the virus to evade immune detection, prevent apoptosis and avoid innate immune response

• latency also means: no viral genome replication and no production of new virus particles

compare lytic vs latent infection

lytic:

• epithelial cells

• viral genes are expressed

• leads to viral replication and production of new virus particles

latent:

• in neuronal cells

• virus persists without producing virions

• infection remains dormant

regulated by chromatin assembly on HSV DNA

how is HSV gene expression regulated?

• lytic: epithelial cells

• - viral genome becomes associated with histones

• chromatin structure allows active transcription of viral genes

• latent: neuronal cells

• viral genome circularises and becomes associated with heterochromatin- silences gene transcription