A novel rodent papillomavirus isolated from anogenital lesions in its natural host

AbstractIn the present work we describe both the prevalence and the histopathologic features of a novel papillomavirus (referred as McPV2) that naturally infects the rodent Mastomys coucha. Viral DNA could be isolated not only from anogenital wart-like lesions but also from healthy tissues (e.g. liver, kidney, spleen and intestine) without apparent signs of infection. Our finding of a second papillomavirus infecting M. coucha, phylogenetically very distant from the previously known MnPV, reinforces the growing view of warm-blooded vertebrates as being hosts for a number of different papilloma virus types that are not necessarily closely related. The histological descriptions of McPV2-associated anogenital lesions provided here, together with earlier knowledge on MnPV-associated skin carcinogenesis, define M. coucha as an excellent system where the link between infection towards malignancy can be studied in molecular, histochemical and immunological terms in immunocompetent animals. The availability of such an in vivo model also offers the unique opportunity to address defined questions about prophylactic and therapeutic strategies against different papillomavirus infections in their natural host. To date, McPV2 is the first rodent papillomavirus found in anogenital lesions

Interference with energy metabolism by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside induces HPV suppression in cervical carcinoma cells and apoptosis in the absence of LKB11

Carcinogenesis is a dynamic and stepwise process, which is accompanied by a variety of somatic and epigenetic alterations in response to a changing microenvironment. Hypoxic conditions will select for cells that have adjusted their metabolic profile and can maintain proliferation by successfully competing for scarce nutritional and oxygen resources. In the present study we have investigated the effects of energy depletion in the context of HPV (human papillomavirus)-induced pathogenesis. We show that cervical carcinoma cell lines are susceptible to undergoing either growth arrest or cell death under conditions of metabolic stress induced by AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside), a known activator of the AMPK (AMP-activated protein kinase). Our results reveal that AICAR treatment leads to a reduced binding affinity of the transcription factor AP-1 (activator protein-1) and in turn to a selective suppression of HPV transcription. Moreover, the outcome of AICAR on proliferation and survival was dependent on p53 activation and the presence of LKB1, the major upstream kinase of AMPK. Using non-malignant LKB1-expressing somatic cell hybrids, which lose expression after tumorigenic segregation, as well as small interfering RNA LKB1 knockdown approaches, we could further demonstrate that expression of LKB1 protects cells from cytotoxicity induced by agents which modulate the ATP/AMP ratio. Since simulation of low energy status can selectively eradicate LKB1-negative cervical carcinoma cells, AICAR may represent a novel drug in the treatment of cervical cancer