This author interview is by Dr Serena Delbue and Dr Pasquale Ferrante, of the Department of Biomedical, Surgical and Dental Sciences, University of Milano, Milano, Italy. Their full paper, A Potential Linkage Between the JC and BK Polyomaviruses and Brain and Urinary Tract Tumors: A Review of the Literature, is available for download in Advances in Tumor Virology

First please summarise for readers the content of your article.

The potential association between infectious agents and human tumors is very relevant, since worldwide about 16.1% of cancers are related to the presence of bacteria and/or viruses. We focused our attention on the polyomaviruses, that are small DNA viruses, establishing latency in the human host. The name polyomavirus derived from the Greek roots poly-, which means "many", and -oma, which means "tumours". These viruses were originally isolated in mouse (mPyV) and in monkey (SV40). In 1971 the first human polyomaviruses BK and JC were isolated and subsequently demonstrated to be ubiquitous in the human population. JCV and BKV usually infect the human population during early childhood and primary infection is often asymptomatic. These viruses can remain latent in the kidney cells of the host until reactivation which occurs during immunodepression. JCV causes progressive multifocal leukoencephalopathy (PML) in cases of severe immunodeficiency, generally due to HIV infection, whereas BKV causes nephropathy in patients who have undergone to kidney transplants.

PyVs are also able to induce cell transformation when they infect non-permissive cells where viral replication is not supported; this is in contrast to permissive cells, where the virus can replicate. It has been demonstrated by several in vitro studies that the main factor implicated in cell transformation and tumour development is the early protein LTAg, a multifunctional protein, fundamental for the viral life cycle of polyomaviruses, because it regulates the viral genome replication and gene expression. Because of this, JCV and BKV are considered good candidates for playing a role in the pathogenesis of human tumors.

Consequently, it is not surprising that JCV DNA and BKV DNA has been identified mainly in central nervous system tumors (JCV) and urothelial carcinomas of the renal pelvis, prostate, and bladder as well as renal cell carcinomas (BKV).

In this paper we reviewed the published literature and we described the potential association between JCV and BKV with brain and urinary tract tumors, respectively.

How did you come to be involved in your area of study?

We have been studying JCV and BKV since twenty years ago, and we are interested in the different pathogenic manifestations of their infection in the human population. Our previous studies have provided evidences that JCV genome and proteins could be found in the brain tumoral tissues, and that BKV genome could be found in prostate cancer tissues. However, the significance of these findings is still under debate and the topic deserves in depth-analysis, starting from the detailed study of the published literature on the potential association between human polyomaviruses and different forms of malignancies.

What was previously known about the topic of your article?

The question related to the involvement of viral infections in the development of human tumors is still very controversial. This is due to the fact that the majority of the studies did not provide a definitive and proven association between the virus presence, the transforming mechanism and the cancer onset and/or progression. Consequently, even if a large body of data and results are widely diffused in literature, the knowledge on the viral etiology of the tumors is incomplete.

How has your work in this area advanced understanding of the topic?

Our work summarized and tried to critically analyse all the results that have been so far published regarding the presence and the expression of the genome of JCV and BKV in the clinical specimens collected from patients with CNS and urinary tract tumors, respectively. Our intent was to provide a starting point for further epidemiological studies, given the important role of the viral infections as risk factors for the tumor development in humans.

What do you regard as being the most important aspect of the results reported in the article?

Although a role for JCV and BKV in malignant transformation was proposed more than 40 years ago, and although in vitro studies supported the oncogenic properties of the T Ag protein, there is still insufficient evidence of a casual association between these human PyVs and solid cancer development. To settle this issue, JCV and BKV should fulfill criteria that have been fixed for establishing a causal relationship between a virus and a tumor. These criteria include the detection of the viral genome and/or proteins in cancerous tissues, proven molecular mechanisms for inducing tumorigenesis and consistency of association. So far, there are many doubts regarding the fulfillment of the first and the third criteria. However, despite the "inadequate evidence of carcinogenicity in humans", the WHO International Agency for Cancer Research Monograph Working Group decided to classify JCV and BKV as "possibly carcinogenic to humans", belonging to group 2B, on the basis of the "sufficient evidence in experimental animals". Therefore, only further solid, clear-cut epidemiologic, histopathologic and DNA evidence will ultimately settle this urgent issue and will help to answer the still unsolved question: "Do JCV and BKV cause tumors in the human population?" When a complete understanding is reached, a vaccination approach for the prevention of polyomavirus infection may be proposed.

share on