Herpes Simplex Virus

Question 1

Stages

Answer 1

Attachment
Penetration and Uncoating
Immediate Early Gene Expression
Early Gene Expression
Genome Replication
Late Gene Expression
Assembly
Release

Question 2

Attachment

Answer 2

• Receptor Mediated binding to the viral glycoprotein spikes

- Heparan sulfate proteoglycans plus other receptors have been proposed

Question 3

Penetration and Uncoating

Answer 3

• Direct fusion between the plasma membrane and viral envelope triggered by the binding to the receptor
• dispersal of tegument
• docking of nucleocapsids into nuclear pore complex, and injection of viral DNA into nucleus

Question 4

Immediate Gene Expression

Answer 4

• a-TIF (alpha trans-inducing factor) turns on the expression of the 5 alpha genes, which then code for a different transcription factor
• alpha gene mRNAs are exported to the cytoplasm then translated
• alpha proteins are then imported into the nucleus, which activates transcription of viral Beta and gamma genes and represses their alpha transcription

Question 5

Early Gene Expression

Answer 5

• Beta genes transcribed only in the presence of alpha proteins
• The Beta gene mRNAs are then exported to the cytoplasm and translated
• The Beta gene proteins are then imported into the nucleus for genome replication and some aren’t imported into the nucleus
• The Beta proteins activate gamma gene transcription, directly and indirectly

Question 6

Genome Replication

Answer 6

• The virus codes for everything that it needs for replication through Beta gene products
• Genome replication by rolling circle mechanism is called SIGMA mode
• Replication initiates at defined origins, replication fork only needs to be assembled once
• Rolling circle mechanism generates head to tail concatemers (to chain together)

Question 7

Late Gene Expression

Answer 7

• Gamma genes expressed after onset of DNA replication
  Gamma Proteins repress transcription of alpha and beta genes
• Gamma Genes encode virion structural proteins
  nucleocapsid proteins imported into the nucleus
• a-TIF and other tegument proteins retained in the cytoplasm
• Enveloped spike proteins inserted into RER; most traffic to GOLGI, some traffic to INNER nuclear membrane

Question 8

Assembly

Answer 8

• nucleocapsid assembly occurs in the nucleus and ends with mature virions budded into lumen space of trans-Golgi
• formation of empty nucleocapsid shell (begins with portal, scaffolding proteins to support, and nucleocapsid proteins added to build shell)
• shell-stuffing puts viral DNA into nucleocapsid
  primary envelopment of nucleocapsids at inner nuclear
  membrane and exit of nucleocapsids into cytoplasm
• binding of tegument (tegumentation) to nucleocapsids in cytoplasm
• secondary envelopment as tegumented nucleocapsids bud into lumen of trans-Golgi vesicles to form mature, enveloped virions with spike.

Question 9

Release

Answer 9

• Can Occur by 2 ways:
  
  • cell lysis will release mature, enveloped virions
  • Exocytosis- happens before cell lysis, exocytic vesicles can traffic to the plasma membrane and fuse with it, releasing mature, enveloped virions