THE MAREKS-DISEASE VIRUS (MDV) UNIQUE SHORT REGION - ALPHAHERPESVIRUS-HOMOLOGOUS, FOWLPOX VIRUS-HOMOLOGOUS, AND MDV-SPECIFIC GENES

Despite its previous classification as a gammaherpesvirus, primarily d ue to its lymphotropism, Marek's disease virus (MDV), an oncogenic avi an herpesvirus, is phylogenetically more related to the ''neurotropic' ' alphaherpesviruses, characterized by its prototype, herpes simplex v irus (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 en compassing the entire 11,160-bp-long Us 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 hom ologs exclusive to alphaherpesvirus S component genes. These include M DV counterparts of HSV US1 (ICP22), US2, US3 (a serine-threonine prote in kinase), US6, US7, and US8 (HSV glycoproteins gD, gl, and gE, respe ctively), and US10. Three additional ORFs were identified with no appa rent relation to any sequences currently present in the SwissProt or G enBank/EMBL databases, while a fourth was found to exhibit significant homology to an uncharacterized fowlpox virus (FPV) ORF. Having precis ely identified the IR(s)-U-s and U-s-TR(s) junctions, we have correcte d 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 identifyin g 2 new MDV-specific ORFs (SORF1 and SORF3) and a fowlpox homolog (SOR F2), our sequence analysis of the ''virulent'' GA strain of MDV (vMDV) extends upon that of a 5255bp segment located in the U-s region of th e ''very virulent'' RB1B strain of MDV (vvMDV) (Boss at al., 1991, J. Gen, Virol. 72, 939-947; 949-954). These two sequences were found to e xhibit 99% identity at both nucleotide and predicted amino acid levels . Combined with the fact that MDV U-s sequences failed to show statist ically significant CpG deficiencies, our analysis is consistent with M DV bearing a closer phylogenetic relation to alphaherpesviruses than t o gammaherpesviruses. Because alphaherpesvirus-specific U-s region gen es are primarily nonessential for virus replication, they are thought to be important biological property determinants. Thus, our sequence p rovides a foundation for further MDV studies aimed at resolving the ap parent discrepancy between MDV's genetic and biologic properties. (C) 1995 Academic Press, Inc.