Dataset Information


Immunologic Control of Mus musculus Papillomavirus Type 1.

ABSTRACT: Persistent papillomas developed in ~10% of out-bred immune-competent SKH-1 mice following MusPV1 challenge of their tail, and in a similar fraction the papillomas were transient, suggesting potential as a model. However, papillomas only occurred in BALB/c or C57BL/6 mice depleted of T cells with anti-CD3 antibody, and they completely regressed within 8 weeks after depletion was stopped. Neither CD4+ nor CD8+ T cell depletion alone in BALB/c or C57BL/6 mice was sufficient to permit visible papilloma formation. However, low levels of MusPV1 were sporadically detected by either genomic DNA-specific PCR analysis of local skin swabs or in situ hybridization of the challenge site with an E6/E7 probe. After switching to CD3+ T cell depletion, papillomas appeared upon 14/15 of mice that had been CD4+ T cell depleted throughout the challenge phase, 1/15 of CD8+ T cell depleted mice, and none in mice without any prior T cell depletion. Both control animals and those depleted with CD8-specific antibody generated MusPV1 L1 capsid-specific antibodies, but not those depleted with CD4-specific antibody prior to T cell depletion with CD3 antibody. Thus, normal BALB/c or C57BL/6 mice eliminate the challenge dose, whereas infection is suppressed but not completely cleared if their CD4 or CD8 T cells are depleted, and recrudescence of MusPV1 is much greater in the former following treatment with CD3 antibody, possibly reflecting their failure to generate capsid antibody. Systemic vaccination of C57BL/6 mice with DNA vectors expressing MusPV1 E6 or E7 fused to calreticulin elicits potent CD8 T cell responses and these immunodominant CD8 T cell epitopes were mapped. Adoptive transfer of a MusPV1 E6-specific CD8+ T cell line controlled established MusPV1 infection and papilloma in RAG1-knockout mice. These findings suggest the potential of immunotherapy for HPV-related disease and the importance of host immunogenetics in the outcome of infection.


PROVIDER: S-EPMC4619818 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

Similar Datasets

2014-01-01 | S-EPMC4133403 | BioStudies
2017-01-01 | S-EPMC5512245 | BioStudies
2015-01-01 | S-EPMC4409516 | BioStudies
2013-01-01 | S-EPMC3838223 | BioStudies
2018-01-01 | S-EPMC6204794 | BioStudies
1000-01-01 | S-EPMC6085329 | BioStudies
2012-01-01 | S-EPMC3237644 | BioStudies
2017-01-01 | S-EPMC5331621 | BioStudies
2018-01-01 | S-EPMC5795941 | BioStudies
2019-01-01 | S-EPMC6652751 | BioStudies