The complete genomic DNA sequences of AVNV isolated from Chinese scallops were determined using a PCR amplification strategy that has been used extensively to generate genome sequences for other viruses [41–43]. The genome of AVNV was 210,993 bp in size, which was slightly longer than that of OsHV-1, and had a nucleotide composition of 38.5% G+C, which is also similar to that of OsHV-1 (38.7%) The genome organization consisted of three unique regions and two inverted repeat regions, which was similar as that of OsHV-1  and also similar as that of herpes simplex virus  and human cytomegalovirus . Comparative analysis of sequences revealed that AVNV was highly related, but not identical, to OsHV-1 at the nucleotide and amino acid sequence levels (97% and 94-100%, respectively). In addition, previous reports showed that the two viruses were also similar in epidemiology [36, 46, 47], morphology [25, 33, 34, 48] and histopathology [15, 28, 34, 35]. Based on these results, we propose that AVNV may be a variant of OsHV-1.
Sequence comparisons have become the primary approach for evaluating phylogenetic and taxonomic relationships among herpesviruses and for identifying and assigning newly characterized viruses . Using the C2/C6 PCR primers, several OsHV-1 variants were described in France in clams , Pacific oysters and scallops [27, 28]. This fragment contains a polymorphic microsatellite region consisting of a number of CTA repeats. AVNV has three repeats, whereas OsHV-1 has eight , the variant OsHV-1 μVar has four , another OsHV-1 variant has six , and other French specimens present various numbers of CTA repeats . These observations reinforce the fact that the microsatellite region does display polymorphisms and could be utilized for identifying and differentiating among OsHV-1 variants.
Generally, glycoproteins on the viral envelope bind to specific receptor molecules on the host cell, promoting viral entry into the host cell. For ORF88, encoding a putative glycoprotein [25, 28], the modification of GTG (V, valine) to GCG (A, alanine) in AVNV was also reported in an OsHV-1 variant from French scallops by using the Gp3/Gp4 PCR primers to amplify a part of the ORF . It is possible that the polymorphisms in this region might reflect the host-specific, and this needs further investigation. Nevertheless, the fact that OsHV-1 has more than one host species is different to the situation for most vertebrate herpesviruses, which are thought to have co-evolved or adapted in association with single host species, although exceptions have been described [40, 51]. Upon successful transmission to new host species, viruses usually adapt quickly to the changed immunological environment . One of the mechanisms of adaptation involves amino acid changes, in particular in proteins that may facilitate transmission . Indeed, a number of proteins have been implicated in determining host specificity for various viruses . For instance subtypes of influenza A virus may be distinguished by two surface glycoproteins, and amino acid substitutions may alter receptor binding to permit transmission from humans to birds [55, 56].
In comparison to OsHV-1, AVNV presents a large number of variations including deletions, insertions and substitutions in both coding and non-coding regions. One region located at 60,700-63,350 bp in AVNV is particularly unusual in bearing a large insertion of 2.6 kb compared to the OsHV-1 genome. Several OsHV-1 genotypes have also been described in oysters, scallops and clams based on analysis of various genome regions [27–29, 50, 57]. The finding that OsHV-1 specimens collected from different locations may have similar DNA sequences [50, 57], whereas others collected from the same place showed different genotypes , suggests that particular genotypes may be not distributed geographically. More work on genome sequences analysis of different OsHV-1 genotypes would be useful in defining additionally diagnostic polymorphisms. Moreover, sequencing more OsHV-1 strains from different locations and host species may help to elucidate the biological and pathogenic associations of the various genotypes.