Varicellovirus (taxid:10319)

VIRION

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 embedded in the lipid envelope.

GENOME

Monopartite, linear, dsDNA genome of about 125 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.

Transcription occurs in three steps: immediate-early, early and late. The immediate-early genes are transcribed immediately after infection and ensure the transcription of early genes, which encode the proteins necessary for the viral replication. The late genes mostly encode structural proteins.

ENZYMES

• DNA-dependent DNA polymerase [ORF28F]
• DNA primase [ORF6]
• Tegument deneddylase (Peptidase C76) [ORF22]
• Assemblin (Peptidase S21) [33]
• Kinase [ORF47, 66, ORF52]
• Helicase [ORF51, ORF52, ORF55]
• Endonuclease [17, ORF48]
• Ribonucleoside-diphosphate reductase [ORF19]
• Thymidine kinase [TK]
• Thymidylate synthase [ORF13, ORF18]
• Deoxyuridine 5'-triphosphate nucleotidohydrolase [ORF8]
• Uracil-DNA glycosylase [ORF59]
• Ubiquitin ligase [61]

REPLICATION

NUCLEAR

Lytic replication:

1. Attachment of the viral glycoproteins 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 the 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

Innate immune response inhibition

Varicella virus inhibits the cascade leading to production of interferon-beta by targeting host IRF3 protein. Several viral proteins including ORF61, ORF47 and IE62 prevent IRF3 activation and subsequent induction of IFN-beta expression .

Adaptive immune response inhibition

Infected cells show a decrease in MHC class I peptide presentation at the cell surface. Although the mechanism is not fully understood, the ORF66 participates in this process .

Autophagy modulation

Varicella virus does not seem to modulate autophagy that occur in infected cells .

Host shut-off

Varicella-zoster virus IE63 protein represses the basal transcription machinery by disorganizing the pre-initiation complex.

Cell-cycle modulation

The HHV-1 UL24 homolog may inhibit the host cell cycle at the G2/M transition since UL24 from alpha-, beta-, and gammaherpesvirus all inhibit host cell cycle through inactivation of the cyclinB/cdc2 complex .

Apoptosis modulation

The viral protein ORF12 protein triggers phosphorylation of host ERK1/2 and inhibits apoptosis. In neurons, ORF63 also participates in the inhibition of apoptosis .

Host splicing inhibition

VZV IE4 is an alternative splicing regulator of host mRNA. It may act by binding with SR proteins .