Abrogation of Constitutive and Induced Type I and Type III Interferons and Interferon-Stimulated Genes in Keratinocytes by Canine Papillomavirus 2 E6 and E7.

Sarah Quinlan,Hang Yuan,Jennifer A Luff,Susan May,Ryan Weeks

doi:10.3390/v12060677

Abstract

Cutaneous papillomaviruses can cause severe, persistent infections and skin cancer in immunodeficient patients, including people with X-linked severe combined immunodeficiency (XSCID). A similar phenotype is observed in a canine model of XSCID; these dogs acquire severe cutaneous papillomavirus infections that can progress to cancer in association with canine papillomavirus type 2 (CPV2). This canine model system provides a natural spontaneous animal model for investigation of papillomavirus infections in immunodeficient patients. Currently, it is unknown if CPV2 can subvert the innate immune system and interfere with its ability to express antiviral cytokines, which are critical in the host defense against viral pathogens. The aim of the current study was to determine if the oncogenes E6 and E7 from CPV2 interfere with expression of antiviral cytokines in keratinocytes, the target cells of papillomavirus infections. We determined that E6 but not E7 interferes with the constitutive expression of some antiviral cytokines, including interferon (IFN)-β and the IFN-stimulated gene IFIT1. Both E6 and E7 interfere with the transcriptional upregulation of the antiviral cytokines in response to stimulation with the dsDNA Poly(dA:dT). In contrast, while E6 also interferes with the transcriptional upregulation of antiviral cytokines in response to stimulation with the dsRNA Poly(I:C), E7 interferes with only a subset of these antiviral cytokines. Finally, we demonstrated that E7 but not E6 abrogates signaling through the type I IFN receptor. Taken together, CPV2 E6 and E7 both impact expression of antiviral cytokines in canine keratinocytes, albeit likely through different mechanisms.

Highlights

Papillomaviruses (PV) are a widely prevalent, heterogeneous group of host restricted and epitheliotropic viruses within the Papillomaviridae family [1,2]
To investigate if a similar effect is seen for canine papillomavirus type 2 (CPV2), canine keratinocytes expressing E6 or E7 genes were generated using retrovirus transduction
In the canine keratinocytes that expressed CPV2 E6 or E7, we found that CPV2

Summary

Introduction

Papillomaviruses (PV) are a widely prevalent, heterogeneous group of host restricted and epitheliotropic viruses within the Papillomaviridae family [1,2]. They are circular, double stranded, DNA viruses, with a viral genome approximately 8 kb in length [1,2]. The alpha genus comprises those HPV types that infect the mucosal epithelium, and are divided into low-risk types, which cause benign genital warts, and high-risk types, which are associated with the development of cervical cancer as well as other anogenital and oropharyngeal cancers [1,2,3].

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