The structure of Marek disease virus DNA: the presence of unique expansion in nonpathogenic viral DNA.

Abstract

DNA of Marek disease virus (MDV) consists of two unique regions UL and US flanked by long inverted repeat regions TRL and IRL, and short inverted repeat regions TRS and IRS, respectively, similar to herpes simplex virus DNA. Comparison of restriction patterns between pathogenic and nonpathogenic MDV DNA was made to identify a region of viral DNA different between these two types of MDV, as it may be responsible for the tumorigenicity of MDV in chickens. The results indicated that BamHI-D and -H, located at the long inverted repeat regions TRL and IRL, were specifically expanded in nonpathogenic viral DNA. The location of the expanded region has been determined within 1.5 kilobase pairs of the Bgl I/Pst I fragment of BamHI-D and -H, close to the junction between the inverted repeat and the unique region. The possibility that a gene responsible for tumor induction may be disrupted by such expansion has been discussed.

Difference in the meq Gene between Oncogenic and Attenuated Strains of Marek's Disease Virus Serotype 1.

“…One possibility is that the long meq ORF may be located in TRL as the native meq ORF in IRL, as reported for two related MDV-specific phosphoproteins, pp38 and pp24, located in IRL and TRL, respectively [27]. In addition, Fukuchi et al [7] also reported that the 1.5-kb BglI-PstI subfragment of the BamHI-D and -H regions present in TRL and IRL of nonpathogenic but not pathogenic MDV1 had heterogeneity.…”

Antisence Oligonucleotide Complementary to the BamHI-H Gene Family of Marek's Disease Virus Induced Growth Arrest of MDCC-MSB1 Cells in the S-Phase.

“…The search for genes responsible for the oncogenicity of MDV has focused on several genes located within the long internal repeats and the short internal repeats of MDV DNA [13], including the Meq gene (a basicleucine-zipper gene), which is highly expressed in lymphoblastoid tumor cells induced by the MDV [11]: the pp38 gene, which encodes a 38-kilodalton phosphoprotein associated with tumor cells induced by MDV [6,8], and the BamHI-H gene family. The transcripts of the BamHI-H gene family disappear, when virus loses the oncogenicity during serial in vitro passage [10,15,19]. Inhibition of the expression of the BamHI-H gene family by antisense oligonucleotides inhibits the proliferation of MDV-derived lymphoblastoid MSB1 cells [12].…”

“…Comparative analysis of the genomic DNA of oncogenic and attenuated MDV reveals expansion of the homologous BamHI-D and BamHI-H fragments of the attenuated MDV. This expansion results from the amplification of a 132-basepairs (bp) direct repeat sequence in this region after serial passage of oncogenic MDV in cell culture [10,15,19]. Analysis of transcription from this region reveals the presence of a BamHI-H gene family producing several 5' coterminal transcripts of different sizes [4].…”

Genomic Difference of Herpesvirus of Turkeys at Low and High Passage Levels in Culture of O1 and FC126 Strains

“…The nonprotective variants of HVT did not replicate in vivo in chickens, but replicated well in cultured cells. Since serial passages of the oncogenic MDV 1 in cultured cells resulted in a structural change of the viral DNA with simultaneous loss of oncogenicity (2,4,5,7,15,16), the structure of HVT DNA may also change during its serial passages of HVT in cultured cells. However, very little is known about the variable regions on the genomes of various HVT isolates.…”