Animal models of papillomavirus pathogenesis

摘要: Tumorigenesis due to papillomavirus (PV) infection was first demonstrated in rabbits and cattle early last century. Despite the evidence obtained animals, role of viruses human cancer dismissed as irrelevant. It took a paradigm shift late 1970s for some be recognised 'tumour viruses' humans, 1995, more than 60 years after Rous's demonstration CRPV oncogenicity, WHO officially declared that 'HPV-16 HPV-18 are carcinogenic humans'. Experimental studies with animal PVs have been determining factor this decision. Animal studied both agents disease animals models PV infection. In addition study whole vitro proteins contributed greatly understanding mechanisms cell transformation. cause distressing diseases farm companion such teat papillomatosis cattle, equine sarcoids canine oral there is an urgent need understand pathogenesis these problematic infections. Persistent florid cows can lead mastitis, prevent suckling calves make milking impossible; heavily affected culled so occasionally herds. Equine often recurrent untreatable loss valuable animals. Canine very extensive persistent great distress. Thus continuing research biology amply justified. BPVs many model systems which HPV. Induction papillomas their neoplastic progression has experimentally reproduced rabbits, virus-cofactor interactions elucidated systems. With advancements molecular culture techniques, direct HPV become less understandably efforts shifted focus from PVs. However, still areas on will continue provide answers questions pertaining virus biology. One involvement oesophageal bladder humans case BPV cattle. Another site viral latency. Lymphocytes proposed latency but only experiments performed could clarify point. instrumental development vaccines rabbit recently dog all opportunity vaccination natural host. Several anti-HPV vaccines, prophylactic therapeutic, based those developed now clinical trials encouraging results. two proteins, transcriptional regulator E2 oncoprotein E5, among others, elucidation gene control product identified regulator; recently, its association mitotic chromosomes suggested mechanism partition genomes between daughter cells, L2-mediated localisation sub-nuclear compartments PODs believed favour DNA encapsidation. E5 major transforming protein several BPVs. Many function established later validated E5. interacts 16k ductin/subunit c interaction deemed responsible down-regulation gap junction intercellular communication inhibition acidification endomembranes. activates growth receptors numerous kinases, including cdks, down-regulates expression MHC class I. would help establishment by promoting proliferation immune evasion. not tried inE5 possible anti-papillomavirus vaccine. A recent reported mice HPV-16 recombinant adenovirus reduced tumours induced E5-expressing cells. Perhaps instance work should follow potential naturally occurring models.