A Human Tumor Virus Extends its Reach

Abstract

Evaluation of: Meckes DG Jr, Shair KH, Marquitz AR, Kung CP, Edwards RH, Raab-Traub N: Human tumor virus utilizes exosomes for intercellular communication. Proc. Natl Acad. Sci. USA 107(47), 20370–20375 (2010). The article of Meckes et al. evaluated here adds to accumulating evidence that viruses manipulate their environment via the intercellular transfer of viral gene product to recipient cells. The main novelty described in this article is perhaps not that Epstein–Barr virus (EBV)-encoded oncogene latent membrane protein 1 (LMP1) is secreted from tumor cells via small vesicles, but that upon transfer to recipient cells, it activates growth-associated signaling pathways. These vesicles are reminiscent of endocytically-derived exosomes and carry additional cargo besides LMP1, and other important signaling molecules as well. In fact, LMP1 may stimulate the exosomal sorting and secretion of PI3K and EGF receptor proteins by the tumor cells. These signaling molecules are often overexpressed or mutated in epithelial tumors and most notably, when secreted via small vesicles, were shown to have tumorigenic properties outside the cells in which they were produced. Since EBV is a well-known and ubiquitous tumor virus associated with multiple lymphoid and epithelial tumors, these findings may have widespread implications. The authors speculate that EBV-infected tumor cells may impact the growth and survival of neighboring cells in the tumor microenvironment, thus promoting tumor progression.