tailieunhanh - Báo cáo khoa học: Human papillomavirus 16 E7 protein inhibits interferon-c-mediated enhancement of keratinocyte antigen processing and T-cell lysis

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 | ijFEBS Journal Human papillomavirus 16 E7 protein inhibits interferon-y-mediated enhancement of keratinocyte antigen processing and T-cell lysis Fang Zhou Graham R. Leggatt and Ian H. Frazer The University of Queensland Diamantina Institute Princess Alexandra Hospital Brisbane Qld Australia Keywords antigen processing CD8 T cells host-virus interactions papillomavirus Correspondence I. Frazer The University of Queensland Diamantina Institute Princess Alexandra Hospital Ipswich Road Woolloongabba Brisbane Qld 4102 Australia Fax 61 7 3240 5946 Tel 61 7 3240 5310 E-mail Received 14 July 2010 revised 2 December 2010 accepted 10 January 2011 doi 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 -y efficiently enhanced susceptibility to lysis of KCs presenting OVA but not of E7-KCs similarly presenting OVA. E7-KCs also exhibited impaired IFN-y-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-y of KC sensitivity to T-cell lysis by impairing antigen presentation. Introduction Persistent infection of the cervical epithelium with one of a range of oncogenic human papillomaviruses HPVs can initiate cervical cancer. The majority of high-risk papillomavirus infections of immunocompetent individuals are cleared although this can take up to 4 years and a minority of apparently immunocompetent

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