Keratinocyte antiviral response to Poly(dA:dT) stimulation and papillomavirus infection in a canine model of X-linked severe combined immunodeficiency

• Published in: PloS one Vol. 9; no. 7; p. e102033
• Main Authors: Luff, Jennifer A, Yuan, Hang, Kennedy, Douglas, Schlegel, Richard, Felsburg, Peter, Moore, Peter F
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15-07-2014; Public Library of Science (PLoS)
• Subjects: Animals; Base Sequence; Biological response modifiers; Biology and Life Sciences; Biopsy; Bone marrow; Bone Marrow Transplantation; Cell cycle; Cytokine receptors; Cytokines; Cytokines - genetics; Cytokines - metabolism; Defects; Dermatology; Disease; Disease Models, Animal; Dogs; Female; Gene Expression; Gene Expression Regulation - drug effects; Human papillomavirus; Immune response; Immune system; Immunology; Infection; Infections; Interferon; Interferon Regulatory Factors - genetics; Interferon Regulatory Factors - metabolism; Interleukin; Interleukin 15; Interleukin 21; Interleukin 4; Interleukin 7; Interleukin 9; Interleukin Receptor Common gamma Subunit - chemistry; Interleukin Receptor Common gamma Subunit - genetics; Keratinocytes; Keratinocytes - drug effects; Keratinocytes - metabolism; Keratinocytes - virology; Laboratory animals; Molecular Sequence Data; Mutation; Neoplasms; Papillomaviridae; Papillomavirus; Papillomavirus infections; Papillomavirus Infections - drug therapy; Papillomavirus Infections - etiology; Pathology; Patients; Photovoltaic cells; Poly dA-dT - administration & dosage; Poly dA-dT - pharmacology; Polymerase chain reaction; Primary Cell Culture; Proteins; Psoriasis; Receptors; Recovery of function; RNA, Messenger - genetics; Severe combined immunodeficiency; Solar cells; Studies; Transplants; Transplants & implants; Veterinary colleges; Veterinary medicine; Viral infections; Virology; X-Linked Combined Immunodeficiency Diseases - complications; X-Linked Combined Immunodeficiency Diseases - genetics; X-Linked Combined Immunodeficiency Diseases - immunology; X-Linked Combined Immunodeficiency Diseases - therapy; Washington DC; California; United States > US; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0102033

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.