Biology Reference
In-Depth Information
In HCMV, 12 gene families have been identified (Chee et al. 1990; Rigoutsos
et al. 2003; Lesniewski et al. 2006), which have likely arisen by duplication events.
One example is the UL12 family, which consists of ten contiguous genes, US12-
US21 (Lesniewski et al. 2006). After the primordial duplication event, members of
gene families have functionally diverged as the virus has continued to evolve.
In some cases, genes with similar functions reside in close proximity to each
other on the viral genome. As noted above, immune evasion genes are near the
termini, the key immediate-early transcriptional regulatory proteins are derived
from the same transcription unit (UL122, 123) (Stinski and Petrik 2007), genes
known to block apoptosis are grouped (UL36-38) (see the chapter by A.L.
McCormick, this volume), and three genes important for entry into endothelial and
epithelial cells are grouped (UL128-131) (see the chapter by C. Sinzger et al., this
volume). Perhaps these genes have evolved to function in an interactive manner,
and their groupings allow them to generally travel in functional sets as the viral
genome undergoes recombination.
Perspectives
The principal challenge we face in HCMV genomics is to identify the full set of viral
gene products. The majority of larger protein-coding ORFs have certainly been iden-
tified, but there are very likely additional smaller protein-coding ORFs and functional
transcripts that do not serve as mRNAs that remain to be identified.
Finally, it is noteworthy that our knowledge of the HCMV genome relies on the
sequences of a relatively small number of clinical isolates. It remains possible that
variants will be discovered that contain one or more modified genes or additional
genes that will prove to be associated with specific clinical manifestations of viral
infection.
References
Adair R, Liebisch GW, Colberg-Poley AM (2003) Complex alternative processing of human
cytomegalovirus UL37 pre-mRNA. J Gen Virol 84:3353-3358
Adler B, Scrivano L, Ruzcics Z, Rupp B, Sinzger C, Koszinowski U (2006) Role of human
cytomegalovirus UL131A in cell type-specific virus entry and release. J Gen Virol
87:2451-2460
Anders DG, Kacica MA, Pari G, Punturieri SM (1992) Boundaries and structure of human
cytomegalovirus oriLyt, a complex origin for lytic-phase DNA replication. J Virol
66:3373-3384
Bogner E, Radsak K, Stinski MF (1998) The gene product of human cytomegalovirus open read-
ing frame UL56 binds the pac motif and has specific nuclease activity. J Virol 72:2259-2264
Bolovan-Fritts CA, Mocarski ES, Wiedeman JA (1999) Peripheral blood CD14(+) cells from
healthy subjects carry a circular conformation of latent cytomegalovirus genome. Blood
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