KSHV Latency Locus Cooperates with Myc to Drive Lymphoma in Mice

PLoS Pathog. 2015 Sep 1;11(9):e1005135. doi: 10.1371/journal.ppat.1005135. eCollection 2015 Sep.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Animals
  • Carcinogenesis / metabolism
  • Genetic Loci*
  • Hematopoiesis, Extramedullary
  • Herpesvirus 8, Human / genetics
  • Herpesvirus 8, Human / immunology
  • Herpesvirus 8, Human / physiology*
  • Host-Pathogen Interactions*
  • Humans
  • Hyperplasia
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Lymphocytes / pathology
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / virology*
  • Mice, Transgenic
  • Mutation
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Specific Pathogen-Free Organisms
  • Spleen / immunology
  • Spleen / metabolism
  • Spleen / pathology
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Latency*


  • MYC protein, human
  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc
  • Viral Proteins