Roseolovirus

VIRION

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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 200 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' untranslated 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.

REPLICATION

NUCLEAR

Lytic replication:

  1. Attachment of the viral glycoproteins to host receptors mediates endocytosis of the virus into the host cell.
  2. Entry into host cell is still unclear and may depend on the host cell type, i.e. endocytosis versus fusion at the plasma membrane.
  3. The capsid is transported to the nuclear pore where the viral DNA is released into the nucleus.
  4. Occasionally, the viral genome can be integrated in host chromosome thereby creating a latent virus.
  5. Transcription of immediate early genes which promote transcription of early genes and protect the virus against innate host immunity.
  6. Transcription of early viral mRNA by host polymerase II, encoding proteins involved in replication of the viral DNA.
  7. A first round of circular genome amplification occurs by bidirectional replication
  8. Synthesis of linear concatemer copies of viral DNA by rolling circle.
  9. Transcription of late mRNAs by host polymerase II, encoding structural proteins.
  10. 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

The HHV-6 U24 protein downregulates the T-cell receptor complex and impairs T-cell activation.

Cell-cycle modulation

The UL24 protein homolog induces a cell cycle arrest at G2/M transition through inactivation of the host cyclinB/cdc2 complex .

Innate immune response inhibition

HHV-6 protein IE1 interferes with the binding of IRF3 to the IFN-beta promoter, reduces levels of dimerized IRF3 and nucleus-translocated IRF3 in response to activation by TBK1. This inhibiton of the pathway through IRF3 subsequenty prevents the expression IFN-beta.

Host splicing inhibition

HHV-6 UL42 modulates the host mRNA expression by exporting unspliced mRNA, thereby inducing alternative splicing .