Muromegalovirus (taxid:10365)

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 embeded in the lipid envelope.

GENOME

Monopartite, linear, dsDNA genome of about 230 kb predicted to encode more than 170 open reading frames. 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' 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.

ENZYMES

• DNA-dependent DNA polymerase
• DNA primase
• Tegument deneddylase (Peptidase C76)
• Assemblin (Peptidase S21)
• Kinase
• Helicase
• Ribonucleoside-diphosphate reductase
• Uracil-DNA glycosylase

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. 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

Mouse cytomegalovirus (MCMV) uses m152 and m06 encoded proteins to inhibit surface expression of MHC I molecules .

Apoptosis modulation

Murine cytomegalovirus m38.5 protein interacts with host Bax in infected cells and thus inhibits Bax-mediated cell death . The m36 gene product termed M-vICA plays also a role in cell death suppression .

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. MCMV encodes an UL24 homolog that performs this role . In addition, the IE3 protein is able to arrest cell cycle in G1/S transition or in G2/M.

Innate immune response inhibition

HCMV inhibits the cascade leading to production of interferon-beta by targeting host IRF3 protein with the viral pp65 protein. The m157 protein delivers inhibitory signals to NK cell subsets expressing Ly49I or Ly49I-like inhibitory receptors. Another protein, m04 forms complexes with MHC I and escorts them to the cell surface. This mechanism prevents NK cell activation by restoring the "self" signature and allowing the engagement of inhibitory Ly49 receptors on NK cells. Four other MCMV proteins m145, m152, m155 and m138 are involved in the down-modulation of NKG2D ligand expression.

Host splicing inhibition

HCMV UL69 modulates the host mRNA expression by exporting unspliced mRNA, thereby inducing alternative splicing.