Infection of Human Skin Models with Herpes Simplex Virus 1: Accessibility of the Receptor Nectin-1 during Formation or Impairment of Epidermal Barriers Is Restricted by Tight Junctions.

Herpes simplex virus 1 (HSV-1) must overcome epidermal barriers to reach its receptors on keratinocytes and initiate infection in human skin. The cell-adhesion molecule nectin-1, which is expressed in human epidermis, acts as an efficient receptor for HSV-1 but is not within reach of the virus upon exposure of human skin under nonpathological conditions. Atopic dermatitis skin, however, can provide an entry portal for HSV-1 emphasizing the role of impaired barrier functions.

Herpes Simplex Virus 1 Can Bypass Impaired Epidermal Barriers upon Infection of Skin from Atopic Dermatitis Patients.

To infect its human host, herpes simplex virus 1 (HSV-1) must overcome the protective barriers of skin and mucosa. Here, we addressed whether pathological skin conditions can facilitate viral entry via the skin surface and used infection studies to explore viral invasion in atopic dermatitis (AD) skin characterized by disturbed barrier functions. Our focus was on the visualization of the onset of infection in single cells to determine the primary entry portals in the epidermis.

Human Skin Infection with Herpes Simplex Virus 1.

Although herpes simplex virus 1 (HSV-1) is a well-studied virus, how the virus invades its human host via skin and mucosa to reach its receptors and initiate infection remains an open question. For studies of HSV-1 infection in skin, mice have been used as animal models. Murine skin infection can be induced after injection or scratching of the skin, which provides insights into disease pathogenesis but is clearly distinct from the natural entry route in human tissue.

Susceptibility of Human and Murine Dermal Fibroblasts to Herpes Simplex Virus 1 in the Absence and Presence of Extracellular Matrix.

Herpes simplex virus 1 (HSV-1) invades its human host via the skin and mucosa and initiates infection in the epithelium. While human and murine epidermis are highly susceptible to HSV-1, we recently observed rare infected cells in the human dermis and only minor infection efficiency in murine dermis upon infection. Here, we investigated why cells in the dermis are so inefficiently infected and explored potential differences between murine and human dermal fibroblasts.

Infection of Human Skin with Herpes Simplex Virus 1 Reveals Mechanical Wounds as Insufficient Entry Portals via the Skin Surface.

Herpes simplex virus 1 (HSV-1) enters its human host via the skin and mucosa. The open question is how the virus invades this highly protective tissue to approach its receptors in the epidermis and initiate infection. Here, we performed infection studies in human skin to investigate how susceptible the epidermis and dermis are to HSV-1 and whether wounding facilitates viral invasion.

Endocytic Internalization of Herpes Simplex Virus 1 in Human Keratinocytes at Low Temperature.

Herpes simplex virus 1 (HSV-1) can adopt a variety of pathways to accomplish cellular internalization. In human keratinocytes representing the natural target cell of HSV-1, both direct plasma membrane fusion and endocytic uptake have been found. The impact of either pathway in successful infection, however, remains to be fully understood.

Herpes Simplex Virus 1 Can Enter Dynamin 1 and 2 Double-Knockout Fibroblasts.

Dynamin GTPases, best known for their role in membrane fission of endocytic vesicles, provide a target for viruses to be exploited during endocytic uptake. Recently, we found that entry of herpes simplex virus 1 (HSV-1) into skin cells depends on dynamin, although our results supported that viral internalization occurs via both direct fusion with the plasma membrane and via endocytic pathways. To further explore the role of dynamin for efficient HSV-1 entry, we utilized conditional dynamin 1 and dynamin 2 double-knockout (DKO) fibroblasts as an experimental tool.