Iltovirus

VIRION

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Enveloped, spherical to pleomorphic, 120-200 nm in diameter, T=16 icosahedral symmetry. Capsid consists of 162 capsomers and is surrounded by an amorphous tegument. Glycoproteins complexes are embeded in the lipid envelope.

GENOME

Monopartite, linear, dsDNA genome of about 150 kb. The genome contains terminal and internal reiterated sequences. The genome sequence is repeated at one end. Each virion contains multiple isomeric forms of the genome

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' nontranslated 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. There are some non-coding genes.

There are three types of genes: 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. Standing apart are genes expressed during latency.

The viral proteins VHS and ICP27 are involved in shut-off of host protein translation in order to ensure the selective expression of viral proteins versus cellular proteins.

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 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

Cell-cycle modulation

The conserved UL24 family of human alpha, beta and gamma herpesviruses induces a cell cycle arrest at G2/M transition through inactivation of the host cyclinB/cdc2 complex. Iltoviruses encode an UL24 homolog that should fullfill this role.

Host splicing inhibition

PsHV-1 UL54 is an alternative splicing regulator of host mRNA.