The latency-associated nuclear antigen of Kaposi sarcoma-associated herpesvirus induces B cell hyperplasia and lymphoma.
Kaposi sarcoma-associated herpesvirus (KSHV) is a human lymphotropic herpesvirus. It is implicated in B cell neoplasias such as primary effusion lymphoma and multicentric Castleman disease in AIDS patients. The KSHV latency-associated nuclear antigen (LANA) is consistently expressed in all KSHV-associated tumor cells and was shown to bind the tumor suppressor proteins p53 and pRb. To test LANA's contribution to lymphomagenesis in vivo we generated transgenic mice expressing LANA under the control of its own promoter, which is B cell specific. All of the transgenic mice developed splenic follicular hyperplasia due to an expansion of IgM+ IgD+ B cells and showed increased germinal center formation. We also observed lymphomas, implying that LANA can activate B cells and provide the first step toward lymphomagenesis.
Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7290, USA.
Farnaz D
FD
Fakhari
Joseph H
JH
Jeong
Yogita
Y
Kanan
Dirk P
DP
Dittmer
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000502:physiology*; D001402:B-Lymphocytes / Q000473:pathology* / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*
D000956:Antigens, Viral; D009687:Nuclear Proteins; C109540:latency-associated nuclear antigen