Strain-specific properties and T cells regulate the susceptibility to papilloma induction by Mus musculus papillomavirus 1.

The immunocytes that regulate papillomavirus infection and lesion development in humans and animals remain largely undefined. We found that immunocompetent mice with varying H-2 haplotypes displayed asymptomatic skin infection that produced L1 when challenged with 6×1010 MusPV1 virions, the recently...

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Autores principales:	Alessandra Handisurya, Patricia M Day, Cynthia D Thompson, Michael Bonelli, Douglas R Lowy, John T Schiller
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/861fa68cfccd402590b2b2ecbd5fdaf1
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spelling	oai:doaj.org-article:861fa68cfccd402590b2b2ecbd5fdaf12021-11-25T05:46:11ZStrain-specific properties and T cells regulate the susceptibility to papilloma induction by Mus musculus papillomavirus 1.1553-73661553-737410.1371/journal.ppat.1004314https://doaj.org/article/861fa68cfccd402590b2b2ecbd5fdaf12014-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25121947/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The immunocytes that regulate papillomavirus infection and lesion development in humans and animals remain largely undefined. We found that immunocompetent mice with varying H-2 haplotypes displayed asymptomatic skin infection that produced L1 when challenged with 6×1010 MusPV1 virions, the recently identified domestic mouse papillomavirus (also designated "MmuPV1"), but were uniformly resistant to MusPV1-induced papillomatosis. Broad immunosuppression with cyclosporin A resulted in variable induction of papillomas after experimental infection with a similar dose, from robust in Cr:ORL SENCAR to none in C57BL/6 mice, with lesional outgrowth correlating with early viral gene expression and partly with reported strain-specific susceptibility to chemical carcinogens, but not with H-2 haplotype. Challenge with 1×1012 virions in the absence of immunosuppression induced small transient papillomas in Cr:ORL SENCAR but not in C57BL/6 mice. Antibody-induced depletion of CD3+ T cells permitted efficient virus replication and papilloma formation in both strains, providing experimental proof for the crucial role of T cells in controlling papillomavirus infection and associated disease. In Cr:ORL SENCAR mice, immunodepletion of either CD4+ or CD8+ T cells was sufficient for efficient infection and papillomatosis, although deletion of one subset did not inhibit the recruitment of the other subset to the infected epithelium. Thus, the functional cooperation of CD4+ and CD8+ T cells is required to protect this strain. In contrast, C57BL/6 mice required depletion of both CD4+ and CD8+ T cells for infection and papillomatosis, and separate CD4 knock-out and CD8 knock-out C57BL/6 were also resistant. Thus, in C57BL/6 mice, either CD4+ or CD8+ T cell-independent mechanisms exist that can protect this particular strain from MusPV1-associated disease. These findings may help to explain the diversity of pathological outcomes in immunocompetent humans after infection with a specific human papillomavirus genotype.Alessandra HandisuryaPatricia M DayCynthia D ThompsonMichael BonelliDouglas R LowyJohn T SchillerPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 8, p e1004314 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Alessandra Handisurya Patricia M Day Cynthia D Thompson Michael Bonelli Douglas R Lowy John T Schiller Strain-specific properties and T cells regulate the susceptibility to papilloma induction by Mus musculus papillomavirus 1.
description	The immunocytes that regulate papillomavirus infection and lesion development in humans and animals remain largely undefined. We found that immunocompetent mice with varying H-2 haplotypes displayed asymptomatic skin infection that produced L1 when challenged with 6×1010 MusPV1 virions, the recently identified domestic mouse papillomavirus (also designated "MmuPV1"), but were uniformly resistant to MusPV1-induced papillomatosis. Broad immunosuppression with cyclosporin A resulted in variable induction of papillomas after experimental infection with a similar dose, from robust in Cr:ORL SENCAR to none in C57BL/6 mice, with lesional outgrowth correlating with early viral gene expression and partly with reported strain-specific susceptibility to chemical carcinogens, but not with H-2 haplotype. Challenge with 1×1012 virions in the absence of immunosuppression induced small transient papillomas in Cr:ORL SENCAR but not in C57BL/6 mice. Antibody-induced depletion of CD3+ T cells permitted efficient virus replication and papilloma formation in both strains, providing experimental proof for the crucial role of T cells in controlling papillomavirus infection and associated disease. In Cr:ORL SENCAR mice, immunodepletion of either CD4+ or CD8+ T cells was sufficient for efficient infection and papillomatosis, although deletion of one subset did not inhibit the recruitment of the other subset to the infected epithelium. Thus, the functional cooperation of CD4+ and CD8+ T cells is required to protect this strain. In contrast, C57BL/6 mice required depletion of both CD4+ and CD8+ T cells for infection and papillomatosis, and separate CD4 knock-out and CD8 knock-out C57BL/6 were also resistant. Thus, in C57BL/6 mice, either CD4+ or CD8+ T cell-independent mechanisms exist that can protect this particular strain from MusPV1-associated disease. These findings may help to explain the diversity of pathological outcomes in immunocompetent humans after infection with a specific human papillomavirus genotype.
format	article
author	Alessandra Handisurya Patricia M Day Cynthia D Thompson Michael Bonelli Douglas R Lowy John T Schiller
author_facet	Alessandra Handisurya Patricia M Day Cynthia D Thompson Michael Bonelli Douglas R Lowy John T Schiller
author_sort	Alessandra Handisurya
title	Strain-specific properties and T cells regulate the susceptibility to papilloma induction by Mus musculus papillomavirus 1.
title_short	Strain-specific properties and T cells regulate the susceptibility to papilloma induction by Mus musculus papillomavirus 1.
title_full	Strain-specific properties and T cells regulate the susceptibility to papilloma induction by Mus musculus papillomavirus 1.
title_fullStr	Strain-specific properties and T cells regulate the susceptibility to papilloma induction by Mus musculus papillomavirus 1.
title_full_unstemmed	Strain-specific properties and T cells regulate the susceptibility to papilloma induction by Mus musculus papillomavirus 1.
title_sort	strain-specific properties and t cells regulate the susceptibility to papilloma induction by mus musculus papillomavirus 1.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/861fa68cfccd402590b2b2ecbd5fdaf1
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Strain-specific properties and T cells regulate the susceptibility to papilloma induction by Mus musculus papillomavirus 1.

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