6. Human polyomavirus (PoV) can cause cancer, but it is not known exactly how. P

Question

6. Human polyomavirus (PoV) can cause cancer, but it is not known exactly how. PoV integrates into the human DNA in the middle of a gene called MyBPC, which is a myosin binding protein. MyBPs are neither oncogenes nor tumor suppressor genes, though. So we have to form a hypothesis and test it. The figure shows virus insertion into the MyBPC gene. The part of the virus that inserts has a promoter (blue area). It also encodes a gene, VP1, and a short stretch called Agno that might or might not encode a gene. Integration occurs in the VPI sequence, splitting it as shown. When the provirus is transcribed, it produces an mRNA that is a fusion between VP1 and MyBPC. Because this fusion does not maintain the MyBPC's normal reading frame, when the fusion mRNA is translated, a premature stop codon occurs at the location marked by *. 17 19 P1-MYBPC1 Fusion Protein MYBPC1 no MYBPC1 MYBPC1 PoV Pov provirus T1 A. Suggest THREE specific ways in which this viral insertion might cause tumor formation. For each hypothesis, suggest which protein is involved, and what it might be doing to cause tumor formation. B. Now think of a technique that could be used to test each of your three hypotheses. What experiment could you do, and what would you look for to prove or disprove each hypothesis? 17

Explanation / Answer

Polyomavurus is DNA tumor virus with circular genome encoding only 6 protein including 3 capsid protein.

1) virus integrate into host cell genome and transcribed using host cell machinary and produce some gene product that bind with tumor suppressor and inhibit their activity and cause cancer. Large T antigens are early protein . Large T antigen bind to tumor suppressor protein pRb and p53 and inhibit their activity lead to uncontrolled cell proliferation.

2) virus can directly cause DNA damage by inserting their genome into host cell which lead to affecting normal functioning of gene ultimately led to cancer. Small T antigen bind to PP2A and inhibit cell cycle progression and cause oncogenic transformation of cells.

3) protein that are not the part of virion but affect cell cycle progression here agnoprotein is small protein that produce during late infection cycle and localize VP1 in prenuclear space . It also bind with p53 which maintain cell cycle. So it cause cancer by inhibiting cell cycle.

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