Submitted to: Avian Diseases
Publication Type: Peer reviewed journal
Publication Acceptance Date: 12/2/2004
Publication Date: 6/1/2005
Citation: Cui, X., Lee, L.F., Hunt, H.D., Reed, W., Lupiani, B., Reddy, S. 2005. A Marek's disease virus vIL-8 deletion mutant has attenuated virulence and confers protection against challenge with a very virulent plus strain. Avian Diseases. 49(2):199-206. 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 gene. We showed evidence that this substance interacts with the immune system by attracting certain type of cells for MDV infection. We have knocked out the vIL8 gene and showed that the altered virus can be used as a vaccine similarly as effective as the current vaccine in use. This important information will undoubtedly help industry with a possible vaccine for better control of the disease. It also helps scientists in academia better understand the function of this viral gene.
Technical Abstract: Marek's disease virus is a chicken herpesvirus which causes rapid development of T-cell lymphomas in chickens. MDV encoded vIL-8 gene is homologous to the cellular IL-8 genes but its function is not well defined. By deleting the vIL-8 open reading frame from the Md5 strain based MDV cosmid clones, the recombinant MDV rMd5/dvIL-8 was generated. In vivo experiments demonstrated that deletion of vIL-8 attenuated the virulence of the virus and resulted in significantly less gross tumor, including the visceral and nerve, compared to the parental virus. But the revertant virus, rMd5/dvIL-8-RV, which restored the vIL-8 gene into the rMd5/dvIL-8 viral genome, had the same pathological phenotype as the parental virus, rMd5. Moreover, the rMd5/dvIL-8 virus has the ability to protect chickens against challenge with a very virulent plus (vv+MDV) strain, 648A. Further characterizations of the recombinant virus found that rMd5/dvIL-8 virus was impaired in early cytolytic infection in chickens as shown by significantly less B cell cytolysis and activated T cells. All these data taken together, suggest that vIL-8 may be functioning as a chemoattractant for B-cells and activating T-cells in early phase of pathogenesis by attracting target cells for MDV infection and viral replication.