Latent Membrane Protein 1 (LMP1) from Epstein-Barr Virus (EBV) Strains M81 and B95.8 Modulate miRNA Expression When Expressed in Immortalized Human Nasopharyngeal Cells

The Epstein-Barr virus (EBV) is a ubiquitous gamma herpesvirus strongly associated with nasopharyngeal carcinomas, and the viral oncogenicity in part relies on cellular effects of the viral latent membrane protein 1 (LMP1). It was previously described that EBV strains B95.8 and M81 differ in cell tropism and the activation of the lytic cycle. Nonetheless, it is unknown whether LMP1 from these strains have different effects when expressed in nasopharyngeal cells. Thus, herein we evaluated the effects of EBV LMP1 derived from viral strains B95.8 and M81 and expressed in immortalized nasopharyngeal cells NP69(SV40T) in the regulation of 91 selected cellular miRNAs. We found that cells expressing either LMP1 behave similarly in terms of NF-kB activation and cell migration. Nonetheless, the miRs 100-5p, 192-5p, and 574-3p were expressed at higher levels in cells expressing LMP1 B95.8 compared to M81. Additionally, results generated by in silico pathway enrichment analysis indicated that LMP1 M81 distinctly regulate genes involved in cell cycle (i.e., RB1), mRNA processing (i.e., NUP50), and mitochondrial biogenesis (i.e., ATF2). In conclusion, LMP1 M81 was found to distinctively regulate miRs 100-5p, 192-5p, and 574-3p, and the in silico analysis provided valuable clues to dissect the molecular effects of EBV LMP1 expressed in nasopharyngeal cells.

Automated summary

This study evaluated the effects of LMP1 derived from different strains of EBV on miRNA regulation in nasopharyngeal cells. The results showed that different strains of LMP1 led to differential expression of specific miRNAs, and in silico analysis provided insights into the molecular effects of LMP1 expression on cellular processes and signaling pathways.