Severe papillomavirus infection progressing to metastatic squamous cell carcinoma in bone marrow-transplanted X-linked SCID dogs.
Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma chain (gammac) gene and is identical clinically and immunologically to human XSCID, making it a true homologue of the human disease. Bone marrow-transplanted (BMT) XSCID dogs not only engraft donor T cells and reconstitute normal T-cell function but, in contrast to the majority of transplanted human XSCID patients, also engraft donor B cells and reconstitute normal humoral immune function. Shortly after our initial report of successful BMT of XSCID dogs, it soon became evident that transplanted XSCID dogs developed late-onset severe chronic cutaneous infections containing a newly described canine papillomavirus. This is analogous to the late-onset cutaneous papillomavirus infection recently described for human XSCID patients following BMT. Of 24 transplanted XSCID dogs followed for at least 1 year post-BMT, 71% developed chronic canine papillomavirus infection. Six of the transplanted dogs that developed cutaneous papillomas were maintained for >3 1/2 years post-BMT for use as breeders. Four of these six dogs (67%) developed invasive squamous cell carcinoma (SCC), with three of the dogs (75%) eventually developing metastatic SCC, an extremely rare consequence of SCC in the dog. This finding raises the question of whether SCC will develop in transplanted human XSCID patients later in life. Canine XSCID therefore provides an ideal animal model with which to study the role of the gammac-dependent signaling pathway in the response to papillomavirus infections and the progression of these viral infections to metastatic SCC.
Goldschmidt
Michael H
MH
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey St., Philadelphia, PA 19104, USA.
Kennedy
Jeffrey S
JS
Kennedy
Douglas R
DR
Yuan
Hang
H
Holt
David E
DE
Casal
Margret L
ML
Traas
Anne M
AM
Mauldin
Elizabeth A
EA
Moore
Peter F
PF
Henthorn
Paula S
PS
Hartnett
Brian J
BJ
Weinberg
Kenneth I
KI
Schlegel
Richard
R
Felsburg
Peter J
PJ
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology / Q000821:virology; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000662:veterinary / Q000821:virology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000821:virology*; D004285:Dogs; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000662:veterinary / Q000821:virology*; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis / Q000473:pathology; D030361:Papillomavirus Infections / Q000209:etiology / Q000473:pathology / Q000662:veterinary; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000628:therapy / Q000662:veterinary / Q000821:virology*; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000473:pathology / Q000821:virology*; D013601:T-Lymphocytes / Q000473:pathology / Q000821:virology; D013997:Time Factors; D014183:Transplantation, Heterologous