The latency-associated nuclear antigen of Kaposi sarcoma-associated herpesvirus induces B cell hyperplasia and lymphoma
Open Access
- 1 March 2006
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 116 (3), 735-742
- https://doi.org/10.1172/jci26190
Abstract
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.Keywords
This publication has 43 references indexed in Scilit:
- Increased Expression of Germinal Center–Associated Nuclear Protein RNA-Primase Is Associated with LymphomagenesisCancer Research, 2005
- A Lack of DNA Mismatch Repair on an Athymic Murine Background Predisposes to Hematologic MalignancyCancer Research, 2005
- Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus Type 8-Positive Solid LymphomasThe Journal of Molecular Diagnostics, 2005
- The Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus Modulates Cellular Gene Expression and Protects Lymphoid Cells from p16 INK4A-induced Cell Cycle ArrestJournal of Biological Chemistry, 2005
- The Tumor Microenvironment Controls Primary Effusion Lymphoma Growthin VivoCancer Research, 2004
- Tissue Specificity of the Kaposi's Sarcoma-Associated Herpesvirus Latent Nuclear Antigen (LANA/orf73) Promoter in Transgenic MiceJournal of Virology, 2002
- DNA Binding and Modulation of Gene Expression by the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated HerpesvirusJournal of Virology, 2001
- Differential Regulation of the Overlapping Kaposi's Sarcoma-Associated Herpesvirus vGCR (orf74) and LANA (orf73) PromotersJournal of Virology, 2001
- Modulation of Cellular and Viral Gene Expression by the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated HerpesvirusJournal of Virology, 2001
- Sexual Transmission and the Natural History of Human Herpesvirus 8 InfectionNew England Journal of Medicine, 1998