Abstract

The Epstein Barr virus (EBV) is a globally dispersed pathogen involved in several human cancers of B-cell and non-B-cell origin. EBV has been classified into EBV-1 and EBV-2, which have differences in transforming ability. EBV-1 can transform B-cells into LCL more efficiently than EBV-2, and EBV-2 preferentially infects T-cell lymphocytes. The EBNA3A oncoprotein is a transcriptional regulator of virus and host cell genes and is required to transform B-cells. EBNA3A has six peptide motifs called nuclear localization signal (NLS) that ensure nucleocytoplasmic protein trafficking. The presence of multiple NLS has been suggested to enhance EBNA3 function or different speci-ficities in different cell types. However, studies about the NLS variability associated with EBV types are scarce. Based on a systematic sequence analysis considering more than a thousand EBNA3A sequences of EBV from different human clinical manifestations and geographic locations, we found differences in NLSs nucleotide structure among EBV types. Compared with the EBNA3A EBV-1, EBNA3A EBV-2 have two of the six NLS altered, and these mutations were possibly acquired by recombination. These genetic patterns in the NLS associated with EBV-1 and EBV-2 add infor-mation about the traits of EBNA3A in EBV biology.