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Viable deletion mutant of human papovavirus BK that induces insulinomas in hamsters
Abstract:
A plaque morphology mutant (pm-522) of human papovavirus BK, which was rescued from a human papovavirus BK-induced hamster pineocytoma, was characterized and compared with a cloned wild-type virus (wt-501). Mutant pm-522 formed turbid plaques and grew more slowly than wt-501 in human embryonic kidney (HEK) cells. The immunofluorescence assay revealed that more HEK cells underwent abortive infection with pm-522 than with wt-501. Whereas wt-501 induced brain tumors and osteosarcomas, but no insulinomas, in hamsters, pm-522 induced brain tumors and insulinomas. The DNA of pm-522 was found by electrophoresis and electron microscopy to have a deletion (85 +/- 15 base pairs) and an insertion (40 +/- 10 base pairs) between map coordinates 0.708 and 0.725 from the endonuclease EcoRI cleavage site. These results demonstrate the presence of a viable deletion human papovarivus BK mutant capable of inducing insulinomas in hamsters.
Insights
A new human papovavirus BK mutant (pm-522) with a DNA deletion and insertion was identified. This mutant, unlike the wild-type, can induce insulinomas in hamsters, offering insights into viral oncogenesis.
Area of Science:
- Virology
- Molecular Biology
- Oncology
Background:
- Human papovavirus BK (BKV) is known to induce tumors in hamsters.
- Characterization of viral mutants is crucial for understanding oncogenic mechanisms.
Purpose of the Study:
- To characterize a plaque morphology mutant (pm-522) of human papovavirus BK.
- To compare the biological and genetic properties of mutant pm-522 with wild-type BKV (wt-501).
- To investigate the oncogenic potential of mutant pm-522, particularly its ability to induce insulinomas.
Main Methods:
- Plaque morphology assay in human embryonic kidney (HEK) cells.
- Immunofluorescence assay to assess abortive infections.
- Tumor induction studies in hamsters.
- DNA analysis using electrophoresis and electron microscopy to identify mutations.
Main Results:
- Mutant pm-522 exhibited turbid plaques and slower growth in HEK cells compared to wt-501.
- A higher rate of abortive infections was observed with pm-522 in HEK cells.
- While wt-501 induced brain tumors and osteosarcomas, pm-522 induced brain tumors and insulinomas in hamsters.
- Mutant pm-522 DNA contained a deletion (85 ± 15 bp) and an insertion (40 ± 10 bp) between specific map coordinates.
Conclusions:
- A viable deletion mutant of human papovavirus BK (pm-522) was successfully generated and characterized.
- Mutant pm-522 demonstrates an altered biological profile, including the ability to induce insulinomas in hamsters.
- The identified genetic alterations in pm-522 are linked to its modified oncogenic properties.