KSHV Latency Locus Cooperates with Myc to Drive Lymphoma in Mice.
Kaposi sarcoma-associated herpesvirus (KSHV) has been linked to Kaposi sarcoma and B-cell malignancies. Mechanisms of KSHV-induced oncogenesis remain elusive, however, in part due to lack of reliable in vivo models. Recently, we showed that transgenic mice expressing the KSHV latent genes, including all viral microRNAs, developed splenic B cell hyperplasia with 100% penetrance, but only a fraction converted to B cell lymphomas, suggesting that cooperative oncogenic events were missing. Myc was chosen as a possible candidate, because Myc is deregulated in many B cell lymphomas. We crossed KSHV latency locus transgenic (latency) mice to Cα Myc transgenic (Myc) mice. By itself these Myc transgenic mice develop lymphomas only rarely. In the double transgenic mice (Myc/latency) we observed plasmacytosis, severe extramedullary hematopoiesis in spleen and liver, and increased proliferation of splenocytes. Myc/latency mice developed frank lymphoma at a higher rate than single transgenic latency or Myc mice. These data indicate that the KSHV latency locus cooperates with the deregulated Myc pathways to further lymphoma progression.
Department of Microbiology and Immunology, Program in Global Oncology, Lineberger Comprehensive Cancer Center, and Center for AIDS Research, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Sang-Hoon
SH
Sin
Department of Veterinary Medicine, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
Yongbaek
Y
Kim
Department of Microbiology and Immunology, Program in Global Oncology, Lineberger Comprehensive Cancer Center, and Center for AIDS Research, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Anthony
A
Eason
Department of Microbiology and Immunology, Program in Global Oncology, Lineberger Comprehensive Cancer Center, and Center for AIDS Research, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Dirk P
DP
Dittmer
D000483:Alleles; D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism; D056426:Genetic Loci; D006411:Hematopoiesis, Extramedullary; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D006965:Hyperplasia; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008822:Mice, Transgenic; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D017735:Virus Latency
C489427:MYC protein, human; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D014764:Viral Proteins