title: Keratinocyte antiviral response to Poly(dA:dT) stimulation and papillomavirus infection in a canine model of X-linked severe combined immunodeficiency.
abstract: X-linked severe combined immunodeficiency (XSCID) is caused by a genetic mutation within the common gamma chain (γc), an essential component of the cytokine receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21. XSCID patients are most commonly treated with bone marrow transplants (BMT) to restore systemic immune function. However, BMT-XSCID humans and dogs remain at an increased risk for development of cutaneous papillomavirus (PV) infections and their associated neoplasms, most typically cutaneous papillomas. Since basal keratinocytes are the target cell for the initial PV infection, we wanted to determine if canine XSCID keratinocytes have a diminished antiviral cytokine response to poly(dA:dT) and canine papillomavirus-2 (CPV-2) upon initial infection. We performed quantitative RT-PCR for antiviral cytokines and downstream interferon stimulated genes (ISG) on poly(dA:dT) stimulated and CPV-2 infected monolayer keratinocyte cultures derived from XSCID and normal control dogs. We found that XSCID keratinocytes responded similarly to poly(dA:dT) as normal keratinocytes by upregulating antiviral cytokines and ISGs. CPV-2 infection of both XSCID and normal keratinocytes did not result in upregulation of antiviral cytokines or ISGs at 2, 4, or 6 days post infection. These data suggest that the antiviral response to initial PV infection of basal keratinocytes is similar between XSCID and normal patients, and is not the likely source for the remaining immunodeficiency in XSCID patients.
authors.affiliation: Department of Veterinary Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Luff
authors.affiliation: Department of Pathology, Georgetown University Medical School, Washington, D.C., United States of America.
authors.forename: Hang
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Immunology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Douglas
authors.initials: D
authors.lastname: Kennedy
authors.affiliation: Department of Pathology, Georgetown University Medical School, Washington, D.C., United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Schlegel
authors.affiliation: Department of Immunology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Felsburg
authors.affiliation: Department of Veterinary Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Moore
mesh_terms: D000818:Animals; D001483:Base Sequence; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D053631:Interleukin Receptor Common gamma Subunit / Q000737:chemistry / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism* / Q000821:virology; D008969:Molecular Sequence Data; D009154:Mutation; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000188:drug therapy / Q000209:etiology*; D011067:Poly dA-dT / Q000008:administration & dosage / Q000494:pharmacology*; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics; D053632:X-Linked Combined Immunodeficiency Diseases / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000628:therapy
chemical_list: D016207:Cytokines; D050835:Interferon Regulatory Factors; D053631:Interleukin Receptor Common gamma Subunit; D012333:RNA, Messenger; D011067:Poly dA-dT