Species-specific functions of Epstein-Barr virus nuclear antigen 2 (EBNA2) reveal dual roles for initiation and maintenance of B cell immortalization

被引:6
作者
Muhe, Janine [1 ,2 ]
Wang, Fred [1 ,2 ]
机构
[1] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA
[2] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA
关键词
LYMPHOCYTE GROWTH TRANSFORMATION; NUCLEAR-PROTEIN-2 ACIDIC DOMAIN; MOTOR-NEURON PROTEIN; RHESUS LYMPHOCRYPTOVIRUS; ANIMAL-MODEL; SIGNALING PATHWAY; BINDING PROTEIN; HOST-RANGE; IN-VITRO; INFECTION;
D O I
10.1371/journal.ppat.1006772
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Epstein-Barr virus (EBV) and related lymphocryptoviruses (LCV) from non-human primates infect B cells, transform their growth to facilitate life-long viral persistence in the host, and contribute to B cell oncogenesis. Co-evolution of LCV with their primate hosts has led to species- specificity so that LCVs preferentially immortalize B cells from their natural host in vitro. We investigated whether the master regulator of transcription, EBV nuclear antigen 2 (EBNA2), is involved in LCV species-specificity. Using recombinant EBVs, we show that EBNA2 orthologues of LCV isolated from chimpanzees, baboons, cynomolgus or rhesus macaques (rhLCV) cannot replace EBV EBNA2 for the immortalization of human B cells. Thus, LCV species-specificity is functionally linked to viral proteins expressed during latent, growth-transforming infection. In addition, we identified three independent domains within EBNA2 that act through species-specific mechanisms. Importantly, the EBNA2 orthologues and species-specific EBNA2 domains separate unique roles for EBNA2 in the initiation of B cell immortalization from those responsible for maintaining the immortalized state. Investigating LCV species-specificity provides a novel approach to identify critical steps underlying EBV-induced B cell growth transformation, persistent infection, and oncogenesis.
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页数:22
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