INTRODUCTION: Porcine reproductive and respiratory syndrome virus (PRRSV) emerged about 30 years ago and continues to cause major economic losses in the pork industry. The lack of effective modified live vaccines (MLV) allows the pandemic to continue. BACKGROUND AND OBJECTIVE: We have previously shown that wild strains of PRRSV affect the nascent T cell repertoire in the thymus, deplete T cell clones recognizing viral epitopes essential for neutralization, while triggering a chronic, robust, but ineffective antibody response. Therefore, we hypothesized that the current MLV are inappropriate because they cause similar damage and fail to prevent viral-induced dysregulation of adaptive immunity. METHODS: We tested three MLV strains to demonstrate that all have a comparable negative effect on thymocytes in vitro. Further in vivo studies compared the development of T cells in the thymus, peripheral lymphocytes, and antibody production in young piglets. These three MLV strains were used in a mixture to determine whether at least some of them behave similarly to the wild virus type 1 or type 2. RESULTS: Both the wild and MLV strains cause the same immune dysregulations. These include depletion of T-cell precursors, alteration of the TCR repertoire, necrobiosis at corticomedullary junctions, low body weight gain, decreased thymic cellularity, lack of virus-neutralizing antibodies, and production of non-neutralizing anti-PRRSV antibodies of different isotypes. DISCUSSION AND CONCLUSION: The results may explain why the use of current MLV in young animals may be ineffective and why their use may be potentially dangerous. Therefore, alternative vaccines, such as subunit or mRNA vaccines or improved MLV, are needed to control the PRRSV pandemic.

• Klíčová slova
• B lymphocytes, Porcine respiratory and reproductive syndrome virus, T lymphocytes, T-cell precursors, animals, thymocytes,
• MeSH
• atenuované vakcíny MeSH
• imunitní systém MeSH
• prasata MeSH
• protilátky virové MeSH
• reprodukční a respirační syndrom prasat * prevence a kontrola   MeSH
• virus reprodukčního a respiračního syndromu prasat * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• atenuované vakcíny MeSH
• protilátky virové MeSH

National cancer databases document that melanoma is the most aggressive and deadly cutaneous malignancy with worldwide increasing incidence in the Caucasian population. Around 10% of melanomas occur in families. Several germline mutations were identified that might help to indicate individuals at risk for preventive interventions and early disease detection. More than 50% of sporadic melanomas carry mutations in Ras/Raf/mitogen-activated protein kinase (MAPK/MEK) pathway, which may represent aims of novel targeted therapies. Despite advances in targeted therapies and immunotherapies, the outcomes in metastatic tumor are still unsatisfactory. Here, we review animal models that help our understanding of melanoma development and treatment, including non-vertebrate, mouse, swine, and other mammal models, with an emphasis on those with spontaneously developing melanoma. Special attention is paid to the melanoma-bearing Libechov minipig (MeLiM). This original swine model of hereditary metastatic melanoma enables studying biological processes underlying melanoma progression, as well as spontaneous regression. Current histological, immunohistochemical, biochemical, genetic, hematological, immunological, and skin microbiome findings in the MeLiM model are summarized, together with development of new therapeutic approaches based on tumor devitalization. The ongoing study of molecular and immunological base of spontaneous regression in MeLiM model has potential to bring new knowledge of clinical importance.

• Klíčová slova
• MeLiM, animal model, devitalization, genetics, melanoma, mutation, progression, spontaneous regression, swine,
• MeSH
• maligní melanom kůže MeSH
• melanom genetika   MeSH
• miniaturní prasata genetika   MeSH
• modely nemocí na zvířatech MeSH
• nádory kůže genetika   MeSH
• prasata genetika   MeSH
• progrese nemoci MeSH
• sekundární malignity genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH