Submitted to: Proceedings of the National Academy of Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/15/2000
Publication Date: 12/31/2000
Citation: LEE, L.F., WU, P., SUI, D., REN, D., KAMIL, J., KUNG, H.J., WITTER, R.L. THE COMPLETE UL SEQUENCE AND THE OVERALL GENOMIC ORGANIZATION OF THE GA STRAIN OF MAREK'S DISEASE VIRUS. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES. 2000. V. 97. P. 6091-6096. Interpretive Summary: Marek's disease (MD), a virus induced cancer like disease of chickens, is considered a major disease problem in commercial poultry. Vaccination has dramatically reduced the incidence of the disease, but very little is known about the basic mechanisms involved in the induction of disease. The objective of this research was to molecularly characterize the causative virus so that successful programs to control the disease can be developed. We have determined the unique arrangements (sequence) of the genetic building blocks (DNA bases) of the entire virus which contains about 175,000 DNA bases. This unique genetic information of MD virus can code for about 100 hereditary elements (genes) that control important virus functions such as replication and induction of disease. This important genetic information about MD virus will undoubtedly help scientists in acedemia and industry understand the function of the various MD virus genes sand eventually lead to better control of the disease.
Technical Abstract: We have determined the DNA sequence of the Unique Long region (UL) and the Repeat Long (RL) region in the genome of serotype-1 GA strain of Marek's disease virus, a member of alpha herpesvirus. With this information, we can approach the complete nucleotide sequence of GA-MDV. The entire GA-MDV genome is predicted to be about 175 kbp in size, with an organization of TRL-UL-IRL-IRS-US-TRS, typical of alpha herpesvirus. The U sequence contains 113,478 bp and has a base composition of 41.7% G+C. A total of 69 ORFs were identified completely within the UL region, among which 55 are known by comparison to HSV-1. Fourteen of them are novel with presently unknown functions. The sequence of RL reported here together with those published earlier reveal the major structural features of the RL. Virtually all the ORFs encoded by RL are novel and specific to serotype 1 MDV. These ORFs are likely to contribute to some of the unique biological properties of MDV. Among the proteins encoded by MDV-specific ORFs are Meq a jun/fos family of transcriptional factor implicated in transformation and latency, v-IL8, a CXC chemokine, pp38 and pp24, two phosphoproteins with undefined functions. There is also a putative lipase gene (LORF2) which has homologs in SB-1 (serotype II) strain of MDV and in various avian adenoviruses. An additional unique feature of MDV is the presence of LTR remnant sequences of avian retrovirus REV (reticuloendothelisosis virus). These remnant sequences are derived from the U3 enhancer region through ancestral insertions by REV proviruses.