Enveloped, spherical to pleomorphic, 150-200 nm in diameter, T=16 icosahedral symmetry. The capsid consists of 162 capsomers and is surrounded by an amorphous tegument.


Monopartite, linear, dsDNA genome of 152 kb. The genome contains terminal and internal reiterated sequences.


All genes are transcribed by the host RNA polymerase II. and most mRNAs are unspliced. There are three temporal classes of genes: immediate-early (alpha), early (beta) and late (gamma). The immediate-early genes are transcribed immediately after infection to take control of cell defense and to activate early genes. These encode the proteins necessary for the viral DNA replication. The late genes mostly encode structural proteins. Latent genes can stop the replicative process at the early step. Certain proteins are downregulated translationaly by a leaky scanning from an upstream ORF.



Lytic replication:

  1. Attachment of the viral gB, gC, gD and gH proteins to host receptors mediates endocytosis of the virus into the host cell.
  2. Fusion with the plasma membrane to release the core and the tegument proteins into the host cytoplasm.
  3. The capsid is transported to the nuclear pore where viral DNA is released into the nucleus.
  4. Transcription of immediate early genes which promote transcription of early genes and protect the virus against innate host immunity.
  5. Transcription of early viral mRNA by host polymerase II, encoding proteins involved in replication of the viral DNA.
  6. A first round of circular genome amplification occurs by bidirectional replication
  7. Synthesis of linear concatemer copies of viral DNA by rolling circle.
  8. Transcription of late mRNAs by host polymerase II, encoding structural proteins.
  9. Assembly of the virus in nuclear viral factories and budding through the inner lamella of the nuclear membrane which has been modified by the insertion of herpes glycoproteins, throughout the Golgi and final release at the plasma membrane.

Latent replication : replication of circular viral episome in tandem with the host cell DNA using the host cell replication machinery.

Host-virus interaction

Adaptive immune response inhibition

Herpes simplex protein US12 binds specifically to transporters associated with antigen processing (TAP), blocking peptide-binding to TAP and subsequent loading of peptides onto MHC class I molecules . Herpes simplex virus 1 glycoprotein B and US3 collaborate to inhibit CD1d antigen presentation and NKT cell function .

Apoptosis modulation

The viral kinase US3 modulates host apoptosis in different ways. It activates host protein kinase A/PKA to block apoptosis. Additionally, it also interacts with programmed cell death protein 4 (PDCD4) and retains it in the nucleus thereby inhibiting host apoptosis .

Autophagy modulation

Herpes simplex virus ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein and thus blocking host autophagy process .

Cell-cycle modulation

The viral proteins ICP27 and vhs act jointly to repress host gene transcription and blocks the cell cycle at the G1 phase . In addition the UL24 protein induces a cell cycle arrest at G2/M transition through inactivation of the host cyclinB/cdc2 complex .

Innate immune response inhibition

Herpes simplex virus inhibits the cascade leading to production of interferon-beta by targeting different cellular proteins. ICP34.5 forms a complex with host TBK1 and thus disrupts the interaction of TBK1-containing complexes with IRF3 . Another viral protein, ICP0, prevents IRF3 activation and subsequent induction of IFN-beta expression .

Host splicing inhibition

HSV-1 ICP27 is an alternative splicing regulator of host mRNA. It has been shown to act as a splicing silencer at the 3' splice site of the PML intron 7a .