The Early genes 6 and 7 (E6/E7) of the HPV cause perturbation of the p53 and Rbp, respectively. This phenomenon is well-noticed in the SV40 where the large T antigen (TAg) abrogate the functions of the P53 and Rbp as well. However, in HPV the scenario is different because that viral mistake causes cancer whereas in SV40 that does not cause cancer (it may in animals but not in humans).
We know the fact that E6 and E7 have other cellular targets than p53 and Rbp. The TAg also has other targets. So in HPV, is it really about those targets to cause cancer? Or are we looking at the far third-end of the story where the E6 and E7 of the HPV only maintain tumorigenicity based on a feedback loop that was prepared at the beginning by other Early and Late genes of the HPV. Researchers have been investing their times to restore the p53 and Rbp, which indeed a great job to initiate apoptosis but what is the real story beyond that cancer caused by HPV specially when we compare its events to SV40 TAg.
Let's discuss it.
Hi Fawzi,
interesting question and I can not answer it in detail at the moment because I am not familiar with SV40. I see following points:
- humans are not the usual host for SV40, in some animals they cause cancer and can transform cells in culture
- different tissues with varying proliferation capacity infected by these viruses?
- even high-risk HPV causing cancer only in the minority of infections of the genital tract pointing to the requirement of aberrations within the host cell
- HPV seems to be not strictly involved in skin cancer subtypes
- cancer development if the viral life cycle can not be completed?
- differences in immune responses?
...I will think about it in more detail
While I am sure that a thorough proteomics study in an animal model would give many answers, bear in mind the virus only causes cancer as an aberration in its normal lifecycle - integration of the genome - together with a series of other enabling events. Like presence of carcinogens linked to cigarette smoke.
Hello! :-)
For me, the highlights for this discussion are:
1) The E1 replicative helicase of the bovine papillomavirus type 1 (BPV-1) exhibits a similar hexameric quaternary structure. Superimposition of the L-Tag and E1 assemblies shows how close the machinery of DNA unwinding is between polyoma- and papillomaviruses.
2) Polyoma- and papillomavirus helicases adopt a hexameric form to unwind the viral DNA. The SV40 L-Tag helicase domain shares 10% (110 residues) and 11% (72 residues) of sequence identity with BPV-1 and HPV16 E1, respectively. However, a percentage of similarity of 18% (197 residues) and 34% (245 residues) with BPV-1 and HPV-16, respectively, indicate a conserved fold and the same degree of oligomerization of the replicative helicases in these two viral families.
3) E6 and E7 share conserved motifs with the L-Tag for the inactivation of p53 and Rb.
4) The helicase domain as a drug target for inhibition of polyomavirus replication: compounds targeting the helicases of polyoma- and papillomavirus are presented.
Thanks to advances in molecular biology, new members of the polyomavirus family have been discovered during the past 5-6 years. The genome organization and the conserved features of their gene products, especially the L-Tag, make interesting targets for the study of this virus family. For example, understanding the mechanism of tumorigenesis due to Merkel cell polyomavirus L-Tag may be helpful for the design of new strategies to manage human cancers in general, and against virus-induced cancers, particularly HPV-related cancers.
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