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

Mark S. Parcells, Su Fang Lin, Robert L. Dienglewicz, Vladimir Majerciak, Dan R. Robinson, Hua Chien Chen, Zining Wu, George R. Dubyak, Peter Brunovskis, Henry D. Hunt, Lucy F. Lee, Hsing-Jien Kung

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118 Scopus citations

Abstract

Chemokines induce chemotaxis, cell migration, and inflammatory responses. We 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 representing the prototype CXC chemokine. The gene for vIL-8 consists of three 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 was detected in an n-butyrate-treated, MDV-transformed T-lymphoblastoid cell line, MSB-1. This induction is essentially abolished by cycloheximide and herpesvirus DNA polymerase inhibitor phosphonoacetate, indicating that vIL-8 is expressed with true late (γ2) kinetics. Baculovirus-expressed vIL-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 for heterophils. To characterize the function of vIL-8 with respect to MDV infection in vivo, a recombinant MDV was constructed with a deletion of all three exons and a soluble-modified green fluorescent protein (smGFP) expression cassette inserted at the site of deletion. In two in vivo experiments, the vIL-8 deletion mutant (RB1BvIL-8δsmGFP) showed a decreased level of lytic infection in comparison to its parent virus, an equal-passage-level parent virus, and to another recombinant MDV containing the insertion of a GFP expression cassette at the nonessential US2 gene. RB1BvIL-8δsmGFP retained oncogenicity, albeit at a greatly reduced level. Nonetheless, we have been able to establish a lymphoblastoid cell line from an RB1BvIL-8δsmGFP-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 level of MDV in vivo lytic infection.

Original languageEnglish (US)
Pages (from-to)5159-5173
Number of pages15
JournalJournal of Virology
Volume75
Issue number11
DOIs
StatePublished - 2001

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ASJC Scopus subject areas

  • Immunology

Cite this

Parcells, M. S., Lin, S. F., Dienglewicz, R. L., Majerciak, V., Robinson, D. R., Chen, H. C., Wu, Z., Dubyak, G. R., Brunovskis, P., Hunt, H. D., Lee, L. F., & Kung, H-J. (2001). 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. Journal of Virology, 75(11), 5159-5173. https://doi.org/10.1128/JVI.75.11.5159-5173.2001