A major role for the minor capsid protein of human papillomavirus type 16 in immune escape.
High-risk human papillomavirus (HPV) infection of the cervical epithelium is causally linked with the generation of cervical cancer. HPV does not activate Langerhans cells (LC), the APC at the site of infection, leading to immune evasion. The HPV protein responsible for inducing this immune escape has not been determined. We demonstrate that LC exposed to the minor capsid protein L2 in HPV16L1L2 virus-like particles do not phenotypically or functionally mature. However, HPV16L1 virus-like particles significantly induce activation of LC. Our data suggest that the L2 protein plays a specific role in the induction of this immune escape of HPV16 through the manipulation of LC. This novel function is the first immune modulating action attributed to the L2 protein and adds significantly to our understanding of the mechanism of HPV immune escape.
Fahey
Laura M
LM
Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA 90033, USA.
Raff
Adam B
AB
Da Silva
Diane M
DM
Kast
W Martin
WM
D036022:Capsid Proteins / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology / Q000378:metabolism
D036022:Capsid Proteins; D016207:Cytokines; C063316:L2 protein, Human papillomavirus type 16; D008070:Lipopolysaccharides; D009856:Oncogene Proteins, Viral; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt