Marek's disease virus-encoded Meq gene is involved in transformation of lymphocytes but is dispensable for replication

  • Blanca Lupiani
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843; Avian Disease and Oncology Laboratory, Agricultural Research Service, East Lansing, MI 48823; College of Agriculture and Natural Resources, University of Delaware, Newark, DE 19717; and Department of Biological Chemistry, School of Medicine, University of California at Davis, UC Davis Cancer Center, Sacramento, CA 95817
  • Lucy F. Lee
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843; Avian Disease and Oncology Laboratory, Agricultural Research Service, East Lansing, MI 48823; College of Agriculture and Natural Resources, University of Delaware, Newark, DE 19717; and Department of Biological Chemistry, School of Medicine, University of California at Davis, UC Davis Cancer Center, Sacramento, CA 95817
  • Xiaoping Cui
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843; Avian Disease and Oncology Laboratory, Agricultural Research Service, East Lansing, MI 48823; College of Agriculture and Natural Resources, University of Delaware, Newark, DE 19717; and Department of Biological Chemistry, School of Medicine, University of California at Davis, UC Davis Cancer Center, Sacramento, CA 95817
  • Isabel Gimeno
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843; Avian Disease and Oncology Laboratory, Agricultural Research Service, East Lansing, MI 48823; College of Agriculture and Natural Resources, University of Delaware, Newark, DE 19717; and Department of Biological Chemistry, School of Medicine, University of California at Davis, UC Davis Cancer Center, Sacramento, CA 95817
  • Amy Anderson
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843; Avian Disease and Oncology Laboratory, Agricultural Research Service, East Lansing, MI 48823; College of Agriculture and Natural Resources, University of Delaware, Newark, DE 19717; and Department of Biological Chemistry, School of Medicine, University of California at Davis, UC Davis Cancer Center, Sacramento, CA 95817
  • Robin W. Morgan
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843; Avian Disease and Oncology Laboratory, Agricultural Research Service, East Lansing, MI 48823; College of Agriculture and Natural Resources, University of Delaware, Newark, DE 19717; and Department of Biological Chemistry, School of Medicine, University of California at Davis, UC Davis Cancer Center, Sacramento, CA 95817
  • Robert F. Silva
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843; Avian Disease and Oncology Laboratory, Agricultural Research Service, East Lansing, MI 48823; College of Agriculture and Natural Resources, University of Delaware, Newark, DE 19717; and Department of Biological Chemistry, School of Medicine, University of California at Davis, UC Davis Cancer Center, Sacramento, CA 95817
  • Richard L. Witter
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843; Avian Disease and Oncology Laboratory, Agricultural Research Service, East Lansing, MI 48823; College of Agriculture and Natural Resources, University of Delaware, Newark, DE 19717; and Department of Biological Chemistry, School of Medicine, University of California at Davis, UC Davis Cancer Center, Sacramento, CA 95817
  • Hsing-Jien Kung
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843; Avian Disease and Oncology Laboratory, Agricultural Research Service, East Lansing, MI 48823; College of Agriculture and Natural Resources, University of Delaware, Newark, DE 19717; and Department of Biological Chemistry, School of Medicine, University of California at Davis, UC Davis Cancer Center, Sacramento, CA 95817
  • Sanjay M. Reddy
    Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843; Avian Disease and Oncology Laboratory, Agricultural Research Service, East Lansing, MI 48823; College of Agriculture and Natural Resources, University of Delaware, Newark, DE 19717; and Department of Biological Chemistry, School of Medicine, University of California at Davis, UC Davis Cancer Center, Sacramento, CA 95817

書誌事項

公開日
2004-08-02
DOI
  • 10.1073/pnas.0404508101
公開者
Proceedings of the National Academy of Sciences

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説明

<jats:p>Marek's disease virus (MDV) causes an acute lymphoproliferative disease in chickens, resulting in T cell lymphomas in visceral organs and peripheral nerves. Earlier studies have determined that the repeat regions of oncogenic serotype 1 MDV encode a basic leucine zipper protein, Meq, which structurally resembles the Jun/Fos family of transcriptional activators. Meq is consistently expressed in MDV-induced tumor cells and has been suggested as the MDV-associated oncogene. To study the function of Meq, we have generated an rMd5ΔMeq virus by deleting both copies of the<jats:italic>meq</jats:italic>gene from the genome of a very virulent strain of MDV. Growth curves in cultured fibroblasts indicated that Meq is dispensable for<jats:italic>in vitro</jats:italic>virus replication.<jats:italic>In vivo</jats:italic>replication in lymphoid organs and feather follicular epithelium was also not impaired, suggesting that Meq is dispensable for lytic infection in chickens. Reactivation of the rMd5ΔMeq virus from peripheral blood lymphocytes was reduced, suggesting that Meq is involved but not essential for latency. Pathogenesis experiments showed that the rMd5ΔMeq virus was fully attenuated in chickens because none of the infected chickens developed Marek's disease-associated lymphomas, suggesting that Meq is involved in lymphocyte transformation. A revertant virus that restored the expression of the<jats:italic>meq</jats:italic>gene, showed properties similar to those of the parental virus, confirming that Meq is involved in transformation but not in lytic replication in chickens.</jats:p>

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