Genetic Patterns Found in the Nuclear Localization Signals (NLSs) Associated with EBV-1 and EBV-2 Provide New Insights into Their Contribution to Different Cell-Type Specificities

LOUISE ZANELLA, MARÍA ELENA REYES, ISMAEL RIQUELME, MICHEL ABANTO, DANIELA LEON, TAMARA VISCARRA, CARMEN ILI, PRISCILLA BREBI

Keywords: phylogeny, recombination, Epstein–Barr virus (EBV), EBV nuclear antigen EBNA 3A (EBNA3A), EBV classification, nuclear localization signal (NLS)

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 their transformative 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 in order to transform B-cells. EBNA3A has six peptide motifs called nuclear localization signals (NLSs) that ensure nucleocytoplasmic protein trafficking. The presence of multiple NLSs has been suggested to enhance EBNA3 function or different specificities 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 structures among EBV types. Compared with the EBNA3A EBV-1, EBNA3A EBV-2 has two of the six NLSs altered, and these mutations were possibly acquired by recombination. These genetic patterns in the NLSs associated with EBV-1 and EBV-2 provide new information about the traits of EBNA3A in EBV biology.

Más información

Título de la Revista: CANCERS
Volumen: 13
Editorial: MDPI Open Access Publishing
Fecha de publicación: 2021
Página de inicio: 1
Página final: 13
Idioma: English
URL: https://www.mdpi.com/2072-6694/13/11/2569