Mechanisms underlying the invasion of HSV-1 in skin and the cellular entry pathways
Herpes simplex virus 1 (HSV-1) invades its human host via skin and mucocutaneous regions to initiate productive infection in the epithelium. 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. This variety of strategies in turn indicates that the virus is highly flexible to the differences in its target cells. Our goal is to demonstrate whether these multiple entry modes play a role in natural target cells by identifying the molecular determinants that mediate HSV‑1 entry in epidermal keratinocytes and dermal fibroblasts.
To reach its receptors and initiate infection, HSV-1 has to invade tissue and overcome the protective barrier provided by the skin and mucosa. We aim to understand how physical skin barriers, signalling pathways, and receptors contribute to the viral entry process. As patients with skin lesions are predisposed to primary and recurrent HSV-1 infections, we hypothesize that efficient viral invasion in vivo most likely relies on pathological conditions that alter epidermal barriers. To dissect the relevance of each barrier for HSV-1 infection, we established an ex vivo infection model of murine and human skin samples, which allows us to explore the initial steps of HSV-1 invasion in epithelia at the cellular level with the focus on physical skin barriers.