Severe papillomavirus infection progressing to metastatic squamous cell carcinoma in bone marrow-transplanted X-linked SCID dogs

Michael H. Goldschmidt, Jeffrey S. Kennedy, Douglas R. Kennedy, Hang Yuan, David E. Holt, Margret L. Casal, Anne M. Traas, Elizabeth A. Mauldin, Peter F Moore, Paula S. Henthorn, Brian J. Hartnett, Kenneth I. Weinberg, Richard Schlegel, Peter J. Felsburg

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Abstract

Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma chain (γc) 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 γc-dependent signaling pathway in the response to papillomavirus infections and the progression of these viral infections to metastatic SCC.

Original languageEnglish (US)
Pages (from-to)6621-6628
Number of pages8
JournalJournal of Virology
Volume80
Issue number13
DOIs
StatePublished - Jul 2006

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X-Linked Combined Immunodeficiency Diseases
severe combined immunodeficiency
Papillomavirus Infections
Papillomaviridae
squamous cell carcinoma
bone marrow
Squamous Cell Carcinoma
Bone Marrow
Dogs
dogs
infection
Canidae
Skin
Tissue Donors
T-Lymphocytes
T-lymphocytes
Papilloma
Virus Diseases
papilloma
human diseases

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Goldschmidt, M. H., Kennedy, J. S., Kennedy, D. R., Yuan, H., Holt, D. E., Casal, M. L., ... Felsburg, P. J. (2006). Severe papillomavirus infection progressing to metastatic squamous cell carcinoma in bone marrow-transplanted X-linked SCID dogs. Journal of Virology, 80(13), 6621-6628. https://doi.org/10.1128/JVI.02571-05

Severe papillomavirus infection progressing to metastatic squamous cell carcinoma in bone marrow-transplanted X-linked SCID dogs. / Goldschmidt, Michael H.; Kennedy, Jeffrey S.; Kennedy, Douglas R.; Yuan, Hang; Holt, David E.; Casal, Margret L.; Traas, Anne M.; Mauldin, Elizabeth A.; Moore, Peter F; Henthorn, Paula S.; Hartnett, Brian J.; Weinberg, Kenneth I.; Schlegel, Richard; Felsburg, Peter J.

In: Journal of Virology, Vol. 80, No. 13, 07.2006, p. 6621-6628.

Research output: Contribution to journalArticle

Goldschmidt, MH, Kennedy, JS, Kennedy, DR, Yuan, H, Holt, DE, Casal, ML, Traas, AM, Mauldin, EA, Moore, PF, Henthorn, PS, Hartnett, BJ, Weinberg, KI, Schlegel, R & Felsburg, PJ 2006, 'Severe papillomavirus infection progressing to metastatic squamous cell carcinoma in bone marrow-transplanted X-linked SCID dogs', Journal of Virology, vol. 80, no. 13, pp. 6621-6628. https://doi.org/10.1128/JVI.02571-05
Goldschmidt, Michael H. ; Kennedy, Jeffrey S. ; Kennedy, Douglas R. ; Yuan, Hang ; Holt, David E. ; Casal, Margret L. ; Traas, Anne M. ; Mauldin, Elizabeth A. ; Moore, Peter F ; Henthorn, Paula S. ; Hartnett, Brian J. ; Weinberg, Kenneth I. ; Schlegel, Richard ; Felsburg, Peter J. / Severe papillomavirus infection progressing to metastatic squamous cell carcinoma in bone marrow-transplanted X-linked SCID dogs. In: Journal of Virology. 2006 ; Vol. 80, No. 13. pp. 6621-6628.
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