2 research outputs found
EpsteināBarr virus in the multiple sclerosis brain: a controversial issueāreport on a focused workshop held in the Centre for Brain Research of the Medical University of Vienna, Austria
Recent epidemiological and immunological studies provide evidence for an association between EpsteināBarr virus infection and multiple sclerosis, suggesting a role of EpsteināBarr virus infection in disease induction and pathogenesis. A key question in this context is whether EpsteināBarr virus-infected B lymphocytes are present within the central nervous system and the lesions of patients with multiple sclerosis. Previous studies on this topic provided highly controversial results, showing EpsteināBarr virus reactivity in B cells in the vast majority of multiple sclerosis cases and lesions, or only exceptional EpsteināBarr virus-positive B cells in rare cases. In an attempt to explain the reasons for these divergent results, a workshop was organized under the umbrella of the European Union FP6 NeuroproMiSe project, the outcome of which is presented here. This report summarizes the current knowledge of EpsteināBarr virus biology and shows that EpsteināBarr virus infection is highly complex. There are still major controversies, how to unequivocally identify EpsteināBarr virus infection in pathological tissues, particularly in situations other than EpsteināBarr virus-driven lymphomas or acute EpsteināBarr virus infections. It further highlights that unequivocal proof of EpsteināBarr virus infection in multiple sclerosis lesions is still lacking, due to issues related to the sensitivity and specificity of the detection methods
HLA class I molecules consistently present internal influenza epitopes
Cytotoxic T lymphocytes (CTL) limit influenza virus replication and prevent morbidity and mortality upon recognition of HLA class I presented epitopes on the surface of virus infected cells, yet the number and origin of the viral epitopes that decorate the infected cell are unknown. To understand the presentation of influenza virus ligands by human MHC class I molecules, HLA-B*0702-presented viral peptides were directly identified following influenza infection. After transfection with soluble class I molecules, peptide ligands unique to infected cells were eluted from isolated MHC molecules and identified by comparative mass spectrometry (MS). Then CTL were gathered following infection with influenza and viral peptides were tested for immune recognition. We found that the class I molecule B*0702 presents 3ā6 viral ligands following infection with different strains of influenza. Peptide ligands derived from the internal viral nucleoprotein (NP(418ā426) and NP(473ā481)) and from the internal viral polymerase subunit PB1 (PB1(329ā337)) were presented by B*0702 following infection with each of 3 different influenza strains; ligands NP(418ā426), NP(473ā481), and PB1(329ā337) derived from internal viral proteins were consistently revealed by class I HLA. In contrast, ligands derived from hemagglutinin (HA) and matrix protein (M1) were presented intermittently on a strain-by-strain basis. When tested for immune recognition, HLA-B*0702 transgenic mice responded to NP(418ā426) and PB1(329ā337) consistently and NP(473ā481) intermittently while ligands from HA and M1 were not recognized. These data demonstrate an emerging pattern whereby class I HLA reveal a handful of internal viral ligands and whereby CTL recognize consistently presented influenza ligands