Herpesviridae

VIRION

image

Enveloped, spherical to pleomorphic, 150-200 nm in diameter, T=16 icosahedral symmetry. Capsid consists of 162 capsomers and is surrounded by an amorphous tegument. Glycoproteins complexes are embed in the lipid envelope.

GENOME

Monopartite, linear, dsDNA genome of 120-240 kb. The genome contains terminal and internal reiterated sequences.

GENE EXPRESSION

Each viral transcript usually encodes a single protein and has a promoter/regulatory sequence, a TATA box, a transcription initiation site, a 5' leader sequence of 30-300 bp (not translated), a 3' non-translated sequence of 10-30 bp, and a poly A signal. There are many gene overlaps. There are only few spliced genes. Some of the expressed ORFs are antisense to each other. Some ORFs can be accessed from more than one promoter. Certain proteins are downregulated translationaly by a leaky scanning from an upstream ORF.

REPLICATION

NUCLEAR

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

Herpesviruses have evolved different strategies to inhibit the host adaptive immune response. For example, 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 . HCMV instead encodes a protein termed US3 that directly binds and inhibits host tapasin.

Apoptosis modulation

Apoptosis is very often modulated (and usually inhibited) by herpesviridae. The mechanisms used can be caspase-dependent such as HCMV vICA that prevents host caspase-8 activation, or can involved the inhibition other cellular proteins involved in apoptosis such as EBV protein BHRF1, a viral homologue of the Bcl-2 that protect the infected cell against apoptosis.

Autophagy modulation

Several herpesvirus are able to inhibit host cell autophagy process , such as HHV-1 ICP34.5 that interacts with Beclin-1 and stop autophagosomes development.

Cell-cycle modulation

The UL24 protein that is present in all herpesvirus subfamilies ( alpha, beta and gamma-herpesviruses) induces a cell cycle arrest at G2/M transition through inactivation of the host cyclinB/cdc2 complex .

Innate immune response inhibition

Herpes viruses inhibit the cascade leading to production of interferon-beta by mainly targeting the host IRF3 protein. Thus, herpes simplex virus, varicella virus, or HCMV all possess proteins to prevent IRF3 activation.

Host splicing inhibition

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

Species

Synonyms

2016 naming1970's namingOther common name
Human alphaherpesvirus 1Human herpesvirus 1 (HHV-1)Herpes simplex virus 1 (HSV-1)
Human alphaherpesvirus 2Human herpesvirus 2 (HHV-2)Herpes simplex virus 2 (HSV-2)
Human alphaherpesvirus 3Human herpesvirus 3 (HHV-3)Varicella Zoster virus (VZV)
Human gammaherpesvirus 4Human herpesvirus 4 (HHV-4)Epstein Barr virus (EBV)
Human betaherpesvirus 5Human herpesvirus 5 (HHV-5)Human cytomegalovirus (HCMV)
Human betaherpesvirus 6AHuman herpesvirus 6A (HHV-6A)
Human betaherpesvirus 6BHuman herpesvirus 6B (HHV-6B)
Human betaherpesvirus 7Human herpesvirus 7 (HHV-7)
Human gammaherpesvirus 8Human herpesvirus 8 (HHV-8)Kaposi syndrome herpesvirus (KSHV)