Human papillomavirus 16 E7 protein inhibits interferon-γ-mediated enhancement of keratinocyte antigen processing and T-cell lysis

Abstract

Infection of epithelium with human papillomavirus (HPV) 16 is generally prolonged, suggesting an ineffective virus-specific immune response, and prolonged infection promotes anogenital cancer. To determine whether poor antigen presentation by HPV-infected keratinocytes (KCs) contributes to prolonged HPV infection, KCs and KCs expressing HPV 16 E7 protein (E7-KCs) were compared for susceptibility to T-cell-mediated lysis directed to ovalbumin (OVA) processed for presentation by the KCs. Interferon (IFN)-γ efficiently enhanced susceptibility to lysis of KCs presenting OVA, but not of E7-KCs similarly presenting OVA. E7-KCs also exhibited impaired IFN-γ-induced upregulation of transcription of major histocompatibility complex class I antigen processing and presentation-associated genes, and of membrane SIINFEKL-H-2Kb complexes. Thus, expression of HPV 16 E7 protein in KCs may inhibit enhancement by IFN-γ of KC sensitivity to T-cell lysis, by impairing antigen presentation. Keratinocytes (KC) and KC expressing human papillomavirus (HPV) 16 E7 protein (E7-KC) were compared for susceptibility to T-cell mediated lysis. Interferon (IFN)-γ enhanced susceptibility to lysis of KC presenting ovalbumin (OVA), but not of E7-KC similarly presenting OVA. E7-KC also exhibited impaired IFN-γ-induced upregulation of transcription of MHC class I antigen processing and presentation-associated genes. Thus, expression of HPV 16 E7 protein in KC may inhibit enhancement by IFN-γ of KC sensitivity to T-cell lysis by impairing antigen presentation. © 2011 The Authors Journal compilation.