Viral transformation and aneuploidy

Abstract

Human tumor viruses are associated with a variety of human malignancies, and it is estimated that 15% of all human cancers have a viral etiology. An abnormality in chromosomal ploidy or aneuploidy is a hallmark of cancers. In normal cells, euploidy is governed by several factors including an intact spindle assembly checkpoint, accurate centrosome duplication, and proper cytokinesis. Viral oncoproteins are suggested to perturb the cellular machineries for chromosomal segregation creating aneuploidy which can lead to the malignant transformation of infected cells. Here, we review in brief some of the mechanisms used by viruses that can cause cellular aneuploidy.

Figure 1

Pathways to aneuploidy. Aneuploidy can be caused by a) improper microtubule attachment to kinetochores with a defect in the SAC; b) abnormal BFB events; c) failure by a cell after mitosis to undergo proper cytokinesis; and d) aberrant amplification of supernumery centrosomes with multipolar mitosis. Other mechanisms not illustrated here are also possible for the genesis of aneuploidy.

Figure 2

An illustration of HTLV-I Tax-induced aneuploidy. Tax interacts with the spindle assembly checkpoint (SAC) protein, hsMAD1, and inhibits its function. Impairment of SAC permits cells to manifest spontaneous occurrence of unbalanced segregations of chromosomes in mitosis. Separately, Tax can bind RanBP1 and Tax1BP2 which regulate centrosome functions. Tax-induced loss of RanBP1/Tax1BP2 function creates supernumerary centrosomes and multipolar mitotic spindles. A putative result of Tax induced aneuploidy is the presentation of multi-lobulated nuclei in ATL cells, also called “flower cells”.