The Immune Response to Eastern Equine Encephalitis Virus Acquired Through Organ Transplantation.

Vanessa Raabe,Lilin Lai,Christina L Gardner,Dongli Wang,Stephanie M Pouch,Pamela J Glass,Crystal W Burke,Ashley E Piper,Yong Xu,Mark J Mulligan,Chris Huerta

doi:10.3389/fmicb.2020.561530

Abstract

The human immune response to eastern equine encephalitis virus (EEEV) infection is poorly characterized due to the rarity of infection. We examined the humoral and cellular immune response to EEEV acquired from an infected donor via liver transplantation. Both binding and highly neutralizing antibodies to EEEV as well as a robust EEEV-specific IgG memory B cell response were generated. Despite triple-drug immunosuppressive therapy, a virus-specific CD4+ T cell response, predominated by interferon-γ production, was generated. T cell epitopes on the E2 envelope protein were identified by interferon-γ ELISpot. Although these results are from a single person who acquired EEEV by a non-traditional mechanism, to our knowledge this work represents the first analysis of the human cellular immune response to EEEV.

Highlights

Eastern equine encephalitis virus (EEEV), an alphavirus in the Togaviridae family, is a rare arboviral infection in North America with only 121 human cases reported in the United States from 2003 to 2016 (Lindsey et al, 2018)
Intracellular cytokine staining was performed under biosafety level (BSL) 2+ conditions on peripheral blood mononuclear cells (PBMCs) collected on day of infection (DOI) 48 to assess for production of interferon γ (IFN-γ), interleukin 2 (IL-2), macrophage inflammatory protein 1β (MIP-1β), and tumor necrosis factor α (TNF-α) in response to stimulation with EEEV antigen, normal suckling mouse brain antigen, or phorbol 12-myristate 13-acetate (PMA) plus ionomycin
A positive individual peptide T cell response from the EEEV patient was defined by an average number of spots at least three times the average number of spots compared to the corresponding healthy control result and the negative control

Summary

INTRODUCTION

Eastern equine encephalitis virus (EEEV), an alphavirus in the Togaviridae family, is a rare arboviral infection in North America with only 121 human cases reported in the United States from 2003 to 2016 (Lindsey et al, 2018). We describe the humoral and cellular immune response to EEEV in the liver transplant recipient, who was a 40 year old woman with a history of autoimmune hepatitis who received her second liver transplant from the donor retrospectively identified as. EEEV was diagnosed on day 8 after transplantation based on positive EEEV IgM antibodies in cerebrospinal fluid. She had poor neurological recovery with repeat imaging demonstrating cerebral vasculitis and died 3 months post-transplantation (Pouch et al, 2018)

MATERIALS AND METHODS

RESULTS

DISCUSSION

ETHICS STATEMENT