Transcriptional regulatory properties of Epstein-Barr virus nuclear antigen 3C are conserved in simian lymphocryptoviruses.
Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA-3C) is a large transcriptional regulator essential for EBV-mediated immortalization of B lymphocytes. We previously identified interactions between EBNA-3C and two cellular transcription factors, J kappa and Spi proteins, through which EBNA-3C regulates transcription. To better understand the contribution of these interactions to EBNA-3C function and EBV latency, we examined whether they are conserved in the homologous proteins of nonhuman primate lymphocryptoviruses (LCVs), which bear a strong genetic and biological similarity to EBV. The homologue of EBNA-3C encoded by the LCV that infects baboons (BaLCV) was found to be only 35% identical in sequence to its EBV counterpart. Of particular significance, this homology localized predominantly to the N-terminal half of the molecule, which encompasses the domains in EBNA-3C that interact with J kappa and Spi proteins. Like EBNA-3C, both BaLCV and rhesus macaque LCV (RhLCV) 3C proteins bound to J kappa and repressed transcription mediated by EBNA-2 through its interaction with J kappa. Both nonhuman primate 3C proteins were also able to activate transcription mediated by the Spi proteins in the presence of EBNA-2. Like EBNA-3C, a domain encompassing the putative basic leucine zipper motif of the BaLCV-3C protein directly interacted with both Spi-1 and Spi-B. Surprisingly, a recently identified motif in EBNA-3C that mediates repression was not identifiable in the BaLCV-3C protein. Finally, although the C terminus of BaLCV-3C bears minimal homology to EBNA-3C, it nonetheless contains a C-terminal domain rich in glutamine and proline that was able to function as a potent transcriptional activation domain, as does the C terminus of EBNA-3C. The conservation of these functional motifs despite poor overall homology among the LCV 3C proteins strongly suggests that the interactions of EBNA-3C with J kappa and Spi do indeed play significant roles in the life cycle of EBV.
Zhao
Bo
B
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Dalbiès-Tran
Rozenn
R
Jiang
Hua
H
Ruf
Ingrid K
IK
Sample
Jeffery T
JT
Wang
Fred
F
Sample
Clare E
CE
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000821:virology; D001483:Base Sequence; D002460:Cell Line; D002472:Cell Transformation, Viral; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens; D005786:Gene Expression Regulation; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D018143:Lymphocryptovirus / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008253:Macaca mulatta / Q000821:virology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010215:Papio / Q000821:virology*; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism
D000956:Antigens, Viral; D004268:DNA-Binding Proteins; C498774:EBNA-3C, epstein-barr virus; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D009687:Nuclear Proteins; C497570:RBPJ protein, human; D014157:Transcription Factors; D014763:Viral Matrix Proteins; C076877:SPIB protein, human