Herpesvirus systematics

Abstract

This paper is about the taxonomy and genomics of herpesviruses. Each theme is presented as a digest of current information flanked by commentaries on past activities and future directions. The International Committee on Taxonomy of Viruses recently instituted a major update of herpesvirus classification. The former family Herpesviridae was elevated to a new order, the Herpesvirales, which now accommodates 3 families, 3 subfamilies, 17 genera and 90 species. Future developments will include revisiting the herpesvirus species definition and the criteria used for taxonomic assignment, particularly in regard to the possibilities of classifying the large number of herpesviruses detected only as DNA sequences by polymerase chain reaction. Nucleotide sequence accessions in primary databases, such as GenBank, consist of the sequences plus annotations of the genetic features. The quality of these accessions is important because they provide a knowledge base that is used widely by the research community. However, updating the accessions to take account of improved knowledge is essentially reserved to the original depositors, and this activity is rarely undertaken. Thus, the primary databases are likely to become antiquated. In contrast, secondary databases are open to curation by experts other than the original depositors, thus increasing the likelihood that they will remain up to date. One of the most promising secondary databases is RefSeq, which aims to furnish the best available annotations for complete genome sequences. Progress in regard to improving the RefSeq herpesvirus accessions is discussed, and insights into particular aspects of herpesvirus genomics arising from this work are reported.

Fig. 1

Amino acid sequence alignment of the C-terminal regions of membrane protein UL56 and membrane protein UL56A from members of the subfamily Alphaherpesvirinae. The sequences are aligned only in the 15 residues at the left, as relationships among the sequences elsewhere are overall not detectable. The locations of PPXY (and related LPPY) motifs are highlighted in light grey, and other conserved residues located in or between the motifs are underlined. Additional PPXY and PPXY-related motifs in the N-terminal regions (indicated by >) are noted in square brackets. Predicted transmembrane domains are highlighted in dark grey. That for GaHV3 is in lower case to indicate that a correction of a putative frameshift (located approximately) was invoked. The total number of residues in each protein is indicated on the right.

Fig. 2

Amino acid sequence alignment of protein US8A from the genus Simplexvirus. Conserved residues are highlighted in grey, and predicted transmembrane domains are boxed.

Fig. 3

Splicing of UL28 and UL29 and identification of the UL30 gene family in the genus Cytomegalovirus. (a) Layout of ORFs in the relevant region of the HHV5 genome (inverted from its standard depiction), with images of ethidium bromide-stained agarose gels showing RT-PCR and 5′-RACE products (sizes in bp) from total cell RNA harvested late during infection of human fibroblast cells by HHV5 strain Merlin. The RT-PCR products in the right panel relate to the region spanning UL28 and UL29 (primers 5-GTCGCCCAGCATGATGCCGTGCAG-3′ and 5′-CTTTCACCGCGTGCGGATTCTCTG-3′; black arrowheads). The 5′-RACE products in the left panel relate to the region upstream from UL30A (primer 5′-TCTACGGAGACCTGACAGCAGTTG-3′; black arrowhead). The mRNA 5′-end upstream from UL30 is marked with a black square (see panel (c) for details. (b) Nucleotide sequence alignment of predicted (confirmed in the case of HHV5) splice donor (/) and acceptor (\) sites flanking the intron linking UL28 and UL29. The italicized line shows the canonical sequences, with critical residues in bold type. (c) The proposed TATA box, mapped mRNA 5′-end and putative non-ATG (ACG) translational initiation codon (INI) for UL30A in HHV5 strain Merlin. The same 5′-end was mapped experimentally for HHV5 strain AD169. (d) Predicted amino acid sequence alignment of the N-terminal portion of the UL30A and UL30 proteins. The lower case residue at the start of the UL30A sequences indicates the proposed encoding of an initiating methionine residue by the non-ATG codon. Residues that are conserved respectively in at least two UL30A sequences and at least one UL30 sequence (or vice versa) are shaded. The C-termini of the proteins are indicated by >.