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Updated: Sep 3, 2025
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Influence of Type I Interferons in Gammaherpesvirus-68 and Its Influence on EAE Enhancement
Ana Citlali Márquez1,2, Carys Croft3, Iryna Shanina1
1Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
Abstract:
Epstein-Barr virus (EBV) has been identified as a putative trigger of multiple sclerosis (MS). Previously, we reported that mice latently infected with murine gammaherpesvirus 68 (γHV-68), the murine homolog to EBV, and induced for experimental autoimmune encephalomyelitis (EAE), developed an enhanced disease more reminiscent of MS. These prior results showed that expression of CD40 on CD11b+CD11c+ cells in latently infected mice was required to prime the strong Th1 response driving disease as well as decreasing Treg frequencies in the periphery and CNS. Subsequent work demonstrated that transfer of B cells from latently infected mice was sufficient to enhance disease. Herein, we show that B cells from infected mice do not need type I IFN signaling to drive a strong Th1 response, yet are important in driving infiltration of the CNS by CD8+ T cells. Given the importance of type I IFNs in MS, we used IFNARko mice in order to determine if type I IFN signaling was important in the enhancement of EAE in latently infected mice. We found that while type I IFNs are important for the control of γHV-68 infection and maintenance of latency, they do not have a direct effect in the development of enhanced EAE.
Insights
Epstein-Barr virus (EBV) infection enhances experimental autoimmune encephalomyelitis (EAE) in mice. B cells from infected mice drive central nervous system inflammation, but type I interferons are not required for this enhanced EAE.
Area of Science:
- Neuroimmunology
- Virology
- Immunology
Background:
- Epstein-Barr virus (EBV) is implicated in multiple sclerosis (MS) pathogenesis.
- Murine gammaherpesvirus 68 (γHV-68) infection in mice enhances experimental autoimmune encephalomyelitis (EAE), mimicking MS.
- Previous studies identified CD40 on myeloid cells and B cell transfer as key factors in enhanced EAE.
Purpose of the Study:
- To investigate the role of type I interferon (IFN) signaling in γHV-68-induced EAE enhancement.
- To determine if B cells require type I IFN signaling to enhance EAE and drive CD8+ T cell infiltration into the central nervous system (CNS).
Main Methods:
- Induction of EAE in γHV-68 latently infected mice, including those lacking type I IFN receptor (IFNARko).
- Assessment of EAE severity, immune cell populations (CD4+, CD8+ T cells, Tregs), and cytokine profiles.
- Transfer of B cells from infected mice to recipient mice.
Main Results:
- B cells from γHV-68 infected mice enhance EAE by promoting CD8+ T cell CNS infiltration, independent of type I IFN signaling.
- Type I IFNs are crucial for controlling γHV-68 infection and maintaining viral latency.
- Type I IFN signaling does not directly influence the development of enhanced EAE in this model.
Conclusions:
- B cells play a significant role in γHV-68-mediated EAE enhancement by facilitating CD8+ T cell entry into the CNS.
- Type I interferons are dispensable for the exacerbation of EAE in latently infected mice, despite their importance in viral control.
