The Marek's disease virus (MDV) unique short region: Alphaherpesvirus-homologous,fowlpox virus-homologous, and MDV-specific genes

Abstract

Despite its previous classification as a gammaherpesvinus, primarily due to its lymphotropism, Marek's disease virus (MDV), an oncogenic avian herpesvirus, is phylogenetically more related to the “neurotropic” alphaherpesviruses, characterized by its prototype, herpes simplex virus (HSV) (Buckmaster et al., 1988, J. Gen. Virol. 69, 2033–2042). In this report we present the DNA sequence of an 11,286-bp DNA segment encompassing the entire 11,160-by-long U s region of the oncogenic avian herpesvirus, Marek's disease virus. Eleven open reading frames (ORFs) likely to code for proteins were identified; of these, 7 represent homologs exclusive to alphaherpesvirus S component genes. These include MDV counterparts of HSV US1 (ICP22), US2, US3 (a serine-threonine protein kinase), US6, US7, and US8 (HSV glycoproteins gD, gl, and gE, respectively), and US10. Three additional ORFs were identified with no apparent relation to any sequences currently present in the SwissProt or GenBank/EMBL databases, while a fourth was found to exhibit significant homology to an uncharacterized fowlpox virus (FPV) ORF. Having precisely identified the IR S-U s and U s- TR s junctions, we have corrected and clarified their previously reported locations. By characterizing genes encoding three new alphaherpesvirus-related homologs (US1, US8, and US10), completing the sequence for a fourth (US7), and identifying 2 new MDV-specific ORFs (SORF1 and SORF3) and a fowlpox homolog (SORF2), our sequence analysis of the “virulent” GA strain of MDV (vMDV) extends upon that of a 5255-bp segment located in the U s region of the “very virulent” RB1 B strain of MDV (vvMDV) (Ross et al., 1991, J. Gen. Virol. 72, 939–947; 949–954). These two sequences were found to exhibit 99% identity at both nucleotide and predicted amino acid levels. Combined with the fact that MDV U s sequences failed to show statistically significant CpG deficiencies, our analysis is consistent with MDV bearing a closer phylogenetic relation to alphaherpesviruses than to gammaherpesviruses. Because alpha herpesvirus-specific U s region genes are primarily nonessential for virus replication, they are thought to be important biological property determinants. Thus, our sequence provides a foundation for further MDV studies aimed at resolving the apparent discrepancy between MDV's genetic and biologic properties.