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 γ 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 NP69SV40T 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.

Viral Carcinogenesis Beyond Malignant Transformation: EBV in the Progression of Human Cancers.

Cancer progression begins when malignant cells colonize adjacent sites, and it is characterized by increasing tumor heterogeneity, invasion and dissemination of cancer cells. Clinically, progression is the most relevant stage in the natural history of cancers. A given virus is usually regarded as oncogenic because of its ability to induce malignant transformation of cells. Nonetheless, oncogenic viruses may also be important for the progression of infection-associated cancers. Recently this hypothesis has been addressed because of studies on the contribution of the Epstein-Barr virus (EBV) to the aggressiveness of nasopharyngeal carcinoma (NPC). Several EBV products modulate cancer progression phenomena, such as the epithelial-mesenchymal transition, cell motility, invasiveness, angiogenesis, and metastasis. In this regard, there are compelling data about the effects of EBV latent membrane proteins (LMPs) and EBV nuclear antigens (EBNAs), as well as nontranslated viral RNAs, such as the EBV-encoded small nonpolyadenylated RNAs (EBERs) and viral microRNAs, notably EBV miR-BARTs. The available data on the mechanisms and players involved in the contribution of EBV infection to the aggressiveness of NPC are discussed in this review. Overall, this conceptual framework may be valuable for the understanding of the contribution of some infectious agents in the progression of cancers.