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

Chemokines induce chemotaxis, cell migration, and inflammatory responses. W e report the identification of an interleukin-8 (IL-8) homolog, termed vIL- 8, encoded within the genome of Marek's disease virus (MDV). The 134-amino- acid vIL-8 shares closest homology to mammalian and avian IL-8, molecules r epresenting the prototype CXC chemokine. The gene for vIL-8 consists of thr ee exons which map to the BamHI-L fragment within the repeats flanking the unique long region of the MDV genome. A 0.7-kb transcript encoding vIL-8 wa s detected in an n-butyrate-treated, MDV-transformed T-lymphoblastoid cell line, MSB-1. This induction is essentially abolished by cycloheximide and h erpesvirus DNA polymerase inhibitor phosphonoacetate, indicating that vIL-8 is expressed with true late (gamma (2)) kinetics. Baculovirus-expressed vI L-8 was found to be secreted into the medium and shown to be functional as a chemoattractant for chicken peripheral blood mononuclear cells but not fo r heterophils. To characterize the function of vIL-8 with respect to MDV in fection in vivo, a recombinant MDV was constructed with a deletion of all t hree exons and a soluble-modified green fluorescent protein (smGFP) express ion cassette inserted at the site of deletion. In two in vivo experiments, the vIL-8 deletion mutant (RB1BvIL-8 Delta smGFP) showed a decreased level of lytic infection in comparison to its parent virus, an equal-passage-leve l parent virus, and to another recombinant MDV containing the insertion of a GFP expression cassette at the nonessential US2 gene. RB1BvIL-8 Delta smG FP retained oncogenicity, albeit at a greatly reduced level. Nonetheless, w e have been able to establish a lymphoblastoid cell line from an RB1BvIL-8 Delta smGFP-induced ovarian lymphoma (MDCC-UA20) and verify the presence of a latent MDV genome lacking vIL-8. Taken together, these data describe the identification and characterization of a chemokine homolog encoded within the MDV genome that is dispensable for transformation but may affect the le vel of MDV in vivo lytic infection.