Depletion of Langerhans cells in human papillomavirus type 16-infected skin is associated with E6-mediated down regulation of E-cadherin.
Human papillomavirus type 16 (HPV16) is an oncogenic virus that causes persistent infections in cervical epithelium. The chronic nature of HPV16 infections suggests that this virus actively evades the host immune response. Intraepithelial Langerhans cells (LC) are antigen-presenting cells that are critical in T-cell priming in response to viral infections of the skin. Here we show that HPV16 infection is directly associated with a reduction in the numbers of LC in infected epidermis. Adhesion between keratinocytes (KC) and LC, mediated by E-cadherin, is important in the retention of LC in the skin. Cell surface E-cadherin is reduced on HPV16-infected basal KC, and this is directly associated with the reduction in numbers of LC in infected epidermis. Expression of a single viral early protein, HPV16 E6, in KC reduces levels of cell surface E-cadherin thereby interfering with E-cadherin-mediated adhesion. Through this pathway, E6 expression in HPV16-infected KC may limit presentation of viral antigens by LC to the immune system, thus preventing the initiation of a cell-mediated immune response and promoting survival of the virus.
Matthews
Kate
K
Virus Research Unit, Department of Microbiology, Malaghan Institute of Medical Research, Wellington School of Medicine, University of Otago, Dunedin, New Zealand.
Leong
Cheng Mee
CM
Baxter
Lindsay
L
Inglis
Emma
E
Yun
Kankatsu
K
Bäckström
B Thomas
BT
Doorbar
John
J
Hibma
Merilyn
M
D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002460:Cell Line; D002584:Cervix Uteri / Q000821:virology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000821:virology*; D007801:Langerhans Cells / Q000473:pathology*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae / Q000472:pathogenicity*; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D012097:Repressor Proteins; D012867:Skin / Q000821:virology*; D002577:Uterine Cervical Diseases / Q000378:metabolism / Q000473:pathology / Q000821:virology
D015820:Cadherins; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins