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Title: MAREK'S DISEASE VIRUS (MDV) ENCODES AN INTERLEUKIN-8 HOMOLOG (VIL-8): CHARACTERIZATION OF THE VIL-8 PROTEIN AND A VIL-8 DELETION MUTANT MDV

Author
item PARCELLS, MARK - UNIVERSITY OF ARKANSAS
item LIN, SU-FANG - CASE WESTERN RESERVE UNIV
item DIENGLEWICZ, ROBERT - UNIVERSITY OF ARKANSAS
item MAJERCIAK, VLADIMIR - SLOVAK ACAD OF SCIENCES
item ROBINSON, DAN - DARTMOUTH MEDICAL SCHOOL
item CHEN, HUA-CHIEN - UNIVERSITY OF ARKANSAS
item WU, ZINING - DARTMOUTH MEDICAL SCHOOL
item DUBYAK, GEORGE - UNIVERSITY OF ARKANSAS
item Hunt, Henry
item Lee, Lucy

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/9/2001
Publication Date: N/A
Citation: N/A

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 discovered a unique sequence (arrangement) of the genetic building blocks (genes) of the virus termed vIL8 which produces a chemical substance similar to the chicken IL8. We showed evidence that this substance interacts with the immune system by attracting certain type of cells for MDV infection. This important genetic information about MD virus will undoubtedly help scientists in academia and industry understand the function of this viral gene and eventually lead to better control of the disease.

Technical Abstract: Chemokines are cytokine molecules that induce chemotaxis, cell migration and inflammatory responses. We report here the identification of a gene for a chemokine designated vIL8 in the genome of Marek's disease virus (MDV). The gene for vIL8 consists of three exons which are mapped to the Bam HI L fragment of the MDV genome. A 0.7 kb transcript encoding vIL8 was detected in an MDV transformed-T lymphoblastoid cell line, MSB-1. Usin rapid amplification of cDNA ends (RACE) and reverse transcription- polymerase chain reaction (RT-PCR), a cDNA of 454 nucleotides was isolated. This cDNA reveals an open reading frame of 134 amino acids starting with an AUG in the proper context. The N-terminal exon encodes a putative signal peptide, with a sequence rich in hydrophobic amino acid residues. The second and third exons are encoding sequences for the mature chemokine, which contains the four properly spaced cysteines, a hallmark of CXC chemokines. Baculovirus-expressed vIL8 was found to be secreted into the media and shown to be functional as a chemoattractant for chicken peripheral blood mononuclear cells, but not heterophils. The discovery of MDV vIL8 adds to a growing list of chemokines encoded by herpesviruses and identifies one of the first few viral CXC chemokines.