Radioactive in situ hybridization for Epstein–Barr virus–encoded small RNA supports presence of Epstein–Barr virus in the multiple sclerosis brain

Abstract

Sir, despite the association between Epstein–Barr virus infection and multiple sclerosis being supported by an increasing number of epidemiological, serological and immunological studies (Ascherio and Munger, 2010; Maghzi et al. , 2011; Pender, 2011), the mechanisms linking increased immune reactivity to this ubiquitous herpes virus to CNS pathology in patients with multiple sclerosis remain to be demonstrated (Lunemann and Munz, 2009; Giovannoni, 2011). A point of contention is whether an active and persistent Epstein–Barr virus infection in the CNS of patients with multiple sclerosis may sustain a detrimental immunopathological response (Pender, 2009; Ascherio and Bar-Or, 2010). In support of this scenario, we have shown high frequencies of Epstein–Barr virus latently infected B cells and more sporadic signs of viral reactivation in post-mortem brain tissue from patients with multiple sclerosis but not patients with other inflammatory neurological diseases (Serafini et al. , 2007, 2010; Aloisi et al. , 2010). Presence of Epstein–Barr virus latently infected cells in active multiple sclerosis brain lesions has been confirmed recently (Tzartos et al. , 2012). In contrast, other groups did not find Epstein–Barr virus in all or the majority of post-mortem multiple sclerosis brain samples analysed (Hilton et al. , 1994; Opsahl and Kennedy, 2007; Willis et al. , 2009; Peferoen et al. , 2010; Sargsyan et al. , 2010; Torkildsen et al. , 2010). As recently discussed in Brain (Lassmann et al. , 2011), no consensus has been reached on technical and interpretation issues relating to the detection of Epstein–Barr virus in the multiple sclerosis brain. Although a variety of techniques [ in situ hybridization for Epstein–Barr virus-encoded small RNA (EBER), immunohistochemistry for Epstein–Barr virus latent and lytic proteins and PCR assays for Epstein–Barr virus nucleic acids] have been used to search …