Item request has been placed!
×
Item request cannot be made.
×
![loading](/sites/all/modules/hf_eds/images/loading.gif)
Processing Request
Herpes simplex virus spreads rapidly in human foreskin, partly driven by chemokine-induced redistribution of Nectin-1 on keratinocytes.
Item request has been placed!
×
Item request cannot be made.
×
![loading](/sites/all/modules/hf_eds/images/loading.gif)
Processing Request
- المؤلفون: Rana, Hafsa; Truong, Naomi R.; Johnson, Blake; Baharlou, Heeva; Herbert, Jason J.; Kandasamy, Sasikaran; Goddard, Robert; Cohen, Ralph C.; Wines, Michael; Nasr, Najla; Harman, Andrew N.; Bertram, Kirstie M.; Sandgren, Kerrie J.; Cunningham, Anthony L.
- المصدر:
PLoS Pathogens; 6/10/2024, Vol. 20 Issue 6, p1-25, 25p
- الموضوع:
- معلومة اضافية
- نبذة مختصرة :
HSV infects keratinocytes in the epidermis of skin via nectin-1. We established a human foreskin explant infection model to investigate HSV entry and spread. HSV1 entry could only be achieved by the topical application of virus via high density microarray projections (HD-MAPs) to the epidermis, which penetrated beyond one third of its thickness, simulating in vivo microtrauma. Rapid lateral spread of HSV1 to a mean of 13 keratinocytes wide occurred after 24 hours and free virus particles were observed between keratinocytes, consistent with an intercellular route of spread. Nectin-1 staining was markedly decreased in foci of infection in the epidermis and in the human keratinocyte HaCaT cell line. Nectin-1 was redistributed, at the protein level, in adjacent uninfected cells surrounding infection, inducible by CCL3, IL-8 (or CXCL8), and possibly CXCL10 and IL-6, thus facilitating spread. These findings provide the first insights into HSV1 entry and spread in human inner foreskin in situ. Author summary: Herpes Simplex Virus (HSV) infects 3.7 billion people globally, leading, in some, to lifelong recurrent disease and co-infection with viruses such as HIV. There is no cure or vaccine. Animal models and in vitro cell lines do not accurately represent the initial events that take place during HSV infection in human genital mucosa. We have successfully established a model of acute HSV-1 infection within explants of human inner foreskin, a common site for sexual transmission. Topical microtrauma penetrating a third of the way into the epidermis was essential for HSV infection, indicating that the two most superficial strata were refractory. There was rapid spread of HSV1 particles through and around epidermal keratinocytes over 24 hours. HSV1 particles also interacted with and were taken up by epidermal Langerhans Cells (LCs) and Dendritic Cells (Epi DCs). Focal HSV1 infection of keratinocytes induced a redistribution of nectin-1, the HSV entry receptor, in a collar surrounding the foci via specific chemokines which further facilitated viral spread. These results provide an insight into the initial events that lead to HSV1 infection and spread within human genital mucosa and defines a time window of opportunity to target the virus before it enters epidermal nerves and becomes latent. [ABSTRACT FROM AUTHOR]
- نبذة مختصرة :
Copyright of PLoS Pathogens is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
No Comments.