Syphilis Reactivates Latent Epstein-Barr Virus Reservoir via Toll-Like Receptor 2 and B-Cell Receptor Activation

Julia R Hirsiger; Philipp S Fuchs; Peter Häusermann; Bojana Müller-Durovic; Thomas Daikeler; Mike Recher; Hans H Hirsch; Luigi Terracciano; Christoph T Berger

doi:10.1093/ofid/ofz317

Syphilis Reactivates Latent Epstein-Barr Virus Reservoir via Toll-Like Receptor 2 and B-Cell Receptor Activation

Open Forum Infect Dis. 2019 Jul 3;6(9):ofz317. doi: 10.1093/ofid/ofz317. eCollection 2019 Sep.

Authors

Affiliations

¹ Translational Immunology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
² Clinical Immunology, Medical Outpatient Unit, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.
³ Department of Dermatology, University Hospital Basel, Basel, Switzerland.
⁴ Immunobiology Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
⁵ Rheumatology Clinic, University Hospital Basel, Basel, Switzerland.
⁶ Immunodeficiency Clinic and Laboratory, Departments of Internal Medicine and Biomedicine, University Hospital Basel, Basel, Switzerland.
⁷ Division Infection Diagnostics, Department Biomedicine, University Hospital Basel, Basel, Switzerland.
⁸ Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
⁹ Institute of Pathology, University Hospital Basel, Basel, Switzerland.

Abstract

Latent Epstein-Barr virus (EBV) infection can clinically reactivate in immunosuppressed individuals causing lymphoproliferative disease and rarely hepatitis. In this study, we provide in vivo and in vitro evidence that Treponema pallidum infection can cause EBV reactivation with hepatitis in an immunocompetent patient. We report the diagnostic challenges and immunological findings of coinciding syphilis and EBV-associated hepatitis. Using an in vitro EBV-reactivation assay, we demonstrate that T pallidum reactivates latent EBV in a Toll-like receptor (TLR)2/B-cell receptor signaling-dependent manner. Epstein-Barr virus-associated reactivation or lymphoproliferation should be considered in infections with pathogens that activate TLR2.

Keywords: EBV; TLR; Treponema pallidum; reactivation; syphilis.