1. The document discusses a MCV biopsy showing lobular hyperplasia of the epidermis resulting in cup-shaped lesions, with enlarged keratinocytes containing inclusion bodies. 2. MCV can be purified from skin biopsies and particles are around 220-450nm in size. Attempts to grow MCV in cell culture have been unsuccessful. 3. MCV only infects humans, shows tropism for epidermal tissue, and causes epidermal dedifferentiation, hyperproliferation, and benign tumor formation through immune evasion and receptor overexpression.

1. MCV biopsy NIH Clinical Center: Bugert and Turner, 1993 www.dartmouth.edu/~thabif/ weeklyclinic111901/..

2. MCV histopathology Lobular hyperplasia of epidermis into the dermis resulting in a cup-shaped lesion. The basal layers appear normal, but the keratinocytes of stratum malpighii become enlarged and acquire eosinophilic inclusion bodies - Henderson-Patterson bodies that contain virus particles. From biopsy; University of Heidelberg: Bugert, 1988

3. MCV in the host cell SEM Shelley and Burmeister, 1986 MCV can be purified in large quantities from skin biopsies

4. MCV virus preparation ELMI: 220- 450 nm filter MCV-HD-18-yellow-Cardiff 5 350 nm MCV-HD-10-red-Cardiff 1 Attempt to grow in cells in culture Abb. 1.1 , Schemazeichnung eines Pockenpartikels Tubuli Nukleosom Lateralkörper Aussenmembran Hülle Core Membran 100nm

5. MCV infection - biological features 1. only human host / no cell culture system 2. epidermal tissue tropism (gene acquisition-adaptation) 3. epidermal dedifferentiation 4. epidermal hyperproliferation-benign tumors 5. immuneevasion : lack of cellular immune response 6. cell receptor overexpression (EGFR and transferrinR) 7. HPV, EBV (analogy to other human epithelial viruses)  EGF receptor 100nm

7. Minucell ® dual perfusion chamber cell culture system Minucell ® -Loop 3 sterile filter medium reservoir peristaltic pump 37 °C heater plate sterile filter Gas expander module sterile filter perfusion chamber sterile filter 3 way valve (injection port) microscopy

8. Emma Smith: Minucell system in operation (Rm. 115) 9/2004 injection / sample port