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

Abstract

Thymus 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 influence of YFV17D immunization on the transcriptional profiles of immunomodulatory genes in thymus, we evaluated the gene expression ofAIRE, FOXP3, H2-Q7(Qa-2/HLA-G),H2-T23(Qa-1/HLA-E),H2-Q10, andH2-K1following immunization with 10,000 LD50of YFV17D in C57BL/6 and BALB/c mice. The YFV17D virus replicated in thymus and induced the expression ofH2-Q7(Qa-2/HLA-G) andH2-T23(Qa-1/HLA-E) transcripts and repressed the expression ofAIREandFOXP3. Transcriptional expression varied according to tissue and mouse strain analyzed. Expression ofH2-T23(Qa-1/HLA-E) andFOXP3was 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.