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Title: MDV ENCODED VIL-8 GENE IS INVOLVED IN EARLY CYTOLYTIC INFECTION BUT DISPENSABLE FOR ESTABLISHMENT OF LATENCY

Author
item CUI, XIAOPING - MICHIGAN STATE UNIV PDI
item Lee, Lucy
item REED, WILLIE - MICHIGAN STATE UNIV PDI
item KUNG, HSING-JIEN - UC DAVIS CANCER CENTER
item REDDY, SANJAY - TEXAS A & M

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/5/2004
Publication Date: 5/1/2004
Citation: Cui, X., Lee, L.F., Reed, W.M., Kung, H., Reddy, S.M. 2004. Marek's disease virus-encoded vIL-8 gene is involved in early cytolytic infection but dispensable for establishment of latency. Journal of Virology. 78:4753-4760.

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 MD virus 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: To study the function of vIL-8 gene, we generated the vIL-8 deleted virus rMd5/ vIL-8 based on MDV cosmid clones. Growth kinetics study showed that vIL-8 gene is dispensable for virus replication in cell culture. In vivo, as evidenced by less viral antigen expression of rMd5/ vIL-8, vIL-8 gene is involved in early cytolytic infections in lymphoid organs but not in virus replication in the feather follicle epithelium. VIL-8 does not appear to be important for virus reactivation or latency entry. Nevertheless, because of the impaired cytolytic infections, the overall transformation efficiency of the vIL-8 deleted virus is much lower, as reflected by the reduced number of transformed cells at 5 week post inoculation and fewer gross tumors. Importantly, the revertant virus that restored the expression of vIL-8 gene also restored the wild type phenotype, indicating the deficient phenotypes are results of vIL-8 deletion. One of the interesting differences between MDV vIL-8 gene and its cellular counterpart is the presence of a "DKR (Asp-Lys-Arg)" motif instead of "ELR (Glu-Leu-Arg)", preceding the invariable CXC motif. To study the significance of this variation, we generated recombinant MDV, rMd5/vIL-8-ELR, carrying "ELR" motif. Both in vitro and in vivo studies revealed that the "DKR" motif is as competent as "ELR" in sustaining the vIL-8 functions.