Transformed fusions

The occasional accidental fusion between somatic cells is probably harmless to an organism, as the resulting cell generally does not divide. But viruses have the ability to create proliferative fused cells, according to Duelli et al. (page 493). The authors wonder whether viruses might thus contribute to carcinogenesis.The authors were studying human fibroblasts expressing the E1A oncogene when they noticed that the cells fused with normal fibroblasts. The fusogenic activity derived from a contaminating retrovirus, Mason-Pfizer monkey virus (MPMV), in the oncogenic cell line. Exosome-like infectious MPMV particles caused fusion between these cells and the normal fibroblasts. It is not known how the virus causes fusion, although the authors show that exosomal tetraspanins are required.

Virus-instigated fusion is not new, but the products of these fusions were oddly proliferative. The group determined that this ability stemmed from the presence of one of several oncogenes and the ability of the virus to fuse two rather than many cells. Fused cells did not proliferate unless one of the partners expressed an oncogene, such as E1A or c-Myc. Mutant p53 tumor suppressor activity in one fusion partner also led to proliferation of fused cells.

Fusion potentially combines the properties of very different cell types, making the behavior of the resulting hybrid highly unpredictable. Their duplicated centrosomes also make them prone to aneuploidy, which is a common feature of cancer cells. Indeed, recent studies showed that tetraploid cells with mutations in a tumor suppressor generated cancerous aneuploid cells (Fujiwara et al. 2005. Nature. 1043–1047).

Whether viruses create proliferative fused cells in an organism is not yet known, but a virus that provides the machinery for both fusion and deregulated cell cycles might be especially dangerous. Therapeutic treatments that involve either viral vector sequences (as in gene therapy) or cell fusion (as in stem cell treatments) should thus be carefully examined for potential cancer-causing side effects.