Research Article
The Attenuated Live Yellow Fever Virus 17D Infects
the Thymus and Induces Thymic Transcriptional Modifications
of Immunomodulatory Genes in C57BL/6 and BALB/C Mice
Breno Luiz Melo-Lima,
1,2,3
Danillo Lucas Alves Espósito,
4
Benedito Antônio Lopes da Fonseca,
4
Luiz Tadeu Moraes Figueiredo,
4
Philippe Moreau,
2,3
and Eduardo Antonio Donadi
1
1
Division of Clinical Immunology, Department of Medicine, Ribeir˜ ao Preto Medical School, University of S˜ ao Paulo,
Avenida Bandeirantes 3900, 14049-900 Ribeir˜ ao Preto, SP, Brazil
2
Commissariat ` a l’Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des T´ erapies Innovantes,
Service de Recherches en H´ emato-Immunologie, Hˆ opital Saint-Louis, 1 avenue Claude Vellefaux, Bˆ atiment Lailler,
75475 Paris Cedex 10, France
3
Universit´ e Paris-Diderot, Sorbonne Paris-Cit´ e, UMR E5, Institut Universitaire d’H´ ematologie, Hˆ opital Saint-Louis,
1 avenue Claude Vellefaux, 75475 Paris Cedex 10, France
4
Virology Research Center, Ribeir˜ ao Preto Medical School, University of S˜ ao Paulo, Avenida Bandeirantes 3900,
14049-900 Ribeir˜ ao Preto, SP, Brazil
Correspondence should be addressed to Breno Luiz Melo-Lima; brenol@usp.br
Received 25 June 2015; Revised 17 August 2015; Accepted 26 August 2015
Academic Editor: Xu-Jie Zhou
Copyright © 2015 Breno Luiz Melo-Lima et al. Tis is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Tymus is involved in induction of self-tolerance in T lymphocytes, particularly due to Aire activity. In peripheral tissues, Treg
cells and immunomodulatory molecules, like the major histocompatibility complex (MHC) class Ib molecules, are essential for
maintenance of autotolerance during immune responses. Viral infections can trigger autoimmunity and modify thymic function,
and YFV17D immunization has been associated with the onset of autoimmunity, being contraindicated in patients with thymic
disorders. Aiming to study the infuence of YFV17D immunization on the transcriptional profles of immunomodulatory genes
in thymus, we evaluated the gene expression of AIRE, FOXP3, H2-Q7 (Qa-2/HLA-G), H2-T23 (Qa-1/HLA-E), H2-Q10, and H2-
K1 following immunization with 10,000 LD
50
of YFV17D in C57BL/6 and BALB/c mice. Te YFV17D virus replicated in thymus
and induced the expression of H2-Q7 (Qa-2/HLA-G) and H2-T23 (Qa-1/HLA-E) transcripts and repressed the expression of AIRE
and FOXP3. Transcriptional expression varied according to tissue and mouse strain analyzed. Expression of H2-T23 (Qa-1/HLA-
E) and FOXP3 was induced in thymus and liver of C57BL/6 mice, which exhibited defective control of viral load, suggesting a
higher susceptibility to YFV17D infection. Since the immunization with YFV17D modulated thymus gene expression in genetically
predisposed individuals, the vaccine may be related to the onset of autoimmunity disorders.
1. Introduction
Autoimmune disorders have a complex and multifactorial
etiopathogenesis, arising from an imbalance between the
mechanisms involved in maintenance of immune tolerance
and those related to the generation of an efective immune
response [1]. Te thymus is the primary lymphoid organ
related to establishment of central tolerance and related to
functional and phenotypical maturation of thymocytes [2].
Te main events in central tolerance of thymocytes are
the positive and negative selections [2, 3], characterized,
respectively, by the maintenance of cortical double-positive
thymocytes that recognize with low afnity/avidity self-
antigens presented by self-histocompatibility molecules and
Hindawi Publishing Corporation
Autoimmune Diseases
Volume 2015, Article ID 503087, 12 pages
http://dx.doi.org/10.1155/2015/503087