Our longterm goal is to understand how HSV-1 penetrates into the epithelium in vivo and initiates infection in keratinocytes. The current knowledge of HSV-1 entry reflects that the virus is able to use a variety of entry modes at least in cell culture. The variety of strategies may in turn indicate, that HSV-1 is highly flexible to adapt to differences of the target cell. The major challenge will be to demonstrate whether these different entry modes play a role in natural target cells such as keratinocytes and furthermore, to elucidate how entry in tissue occurs. Next to keratinocyte cell lines and primary keratinocytes we established a protocol for ex vivo infection of epidermal sheets that allows studying entry into the epidermis of mouse models as well as of human mucosa.

The AcMNPV genome is replicated in the host cell nuclei and viral DNA synthesis takes place in discrete regions. Rearrangement of nuclear structures starts early during infection and finally leads to accumulation of viral proteins and replicating DNA in replication compartments that nearly fill the nucleus. Our goal is to characterize the composition of the replication compartments during the infection cycle and to unravel whether and how the virus uses pre-existing nuclear structures to deposit its genome for transcription and replication. In addition to viral proteins the cellular factor TBP (TATA binding protein) is recruited to growing replication compartments. We aim to understand the mechanism of TBP recruitment next to replicating viral DNA and its functional significance during infection.

AcMNPV-infection of insect cells leads to extensive changes of the actin cytoskeleton. We have identified actin rearrangement-inducing factor 1 (Arif-1) as an early viral gene product that is involved in the remodeling of the actin cytoskeleton early during infection. Our further studies aim to elucidate the mode of action of Arif-1, and the role of Arif-1-induced actin rearrangement during the infection cycle.