Multiple sclerosis (MS) is a widespread neurodegenerative autoimmune disease with unknown etiology. It is increasingly evident that, together with pathogenic T cells, autoreactive B cells are among the major players in MS development. The analysis of myelin neuroantigen‐specific antibody repertoires and their possible cross‐reactivity against environmental antigens, including viral proteins, could shed light on the mechanism of MS induction and progression. A phage display library of single‐chain variable fragments (scFvs) was constructed from blood lymphocytes of patienst with MS as a potential source of representative MS autoantibodies. Structural alignment of 13 clones selected toward myelin basic protein (MBP), one of the major myelin antigens, showed high homology within variable regions with cerebrospinal fluid MS‐associated antibodies as well as with antibodies toward Epstein‐Barr latent membrane protein 1 (LMP1). Three scFv clones showed pronounced specificity to MBP fragments 65–92 and 130–156, similar to the serum MS antibodies. One of these clones, designated E2, in both scFv and full‐size human antibody constructs, was shown to react with both MBP and LMP1 proteins in vitro , suggesting natural cross‐reactivity. Thus, antibodies induced against LMP1 during Epstein‐Barr virus infection might act as inflammatory trigger by reacting with MBP, suggesting molecular mimicry in the mechanism of MS pathogenesis.—Gabibov, A. G., Belogurov, A. A., Jr. Lomakin, Y. A., Zakharova, M. Y., Avakyan, M. E., Dubrovskaya, V. V., Smirnov, I. V., Ivanov, A. S., Molnar, A. A., Gurtsevitch, V. E., Diduk, S. V., Smirnova, K. V., Avalle, B., Sharanova, S. N., Tramontano, A., Friboulet, A., Boyko, A. N., Ponomarenko, N. A., Tikunova, N. V. Combinatorial antibody library from multiple sclerosis patients reveals antibodies that cross‐react with myelin basic protein and EBV antigen. FASEB J. 25, 4211–4221 (2011). www.fasebj.org

Chronic infections caused by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the main risk factors for the development of hepatocellular carcinoma (HCC) in humans. Both viruses cause a...

Germ cell tumors (GCT) are strictly associated with the expression of HERV‐K(HML‐2) proviruses, and the majority of GCT patients produce antibodies to structural proteins of these proviruses. The objective of our study was to determine the significance of the serological response to HERV‐K(HML‐2) Gag and Env proteins for diagnosis, management of GCT patients and estimation of the therapy success. The data document a strong association of HERV‐K(HML‐2) antibodies and the clinical manifestation of the disease and therapy success. HERV‐K(HML‐2) antibodies seem to have an important diagnostic value as well as indicator of chemotherapy success.

Epstein‐Barr virus (EBV) is a human tumour virus that efficiently growth‐transforms primary human B‐lymphocytes in vitro. The viral nuclear antigen 2 (EBNA2) is essential for immortalisation of B‐cells and stimulates viral and cellular gene expression through interaction with DNA‐bound transcription factors. Like its cellular homologue Notch, it associates with the DNA‐bound repressor RBPJκ (CSL/CBF1) thereby converting RBPJκ into the active state. For instance, both EBNA2 and Notch activate the cellular HES1 promoter. In EBV‐transformed lymphocytes, the RNA of the NP9 protein encoded by human endogenous retrovirus HERV‐K(HML‐2) Type 1 is strongly up‐regulated. The NP9 protein is detectable both in EBV‐positive Raji cells, a Burkitt's lymphoma cell line, and in IB4, an EBV‐transformed human lymphoblastoid cell line. NP9 binds to LNX that forms a complex with the Notch regulator Numb. Therefore, the function of NP9 vis‐à‐vis Notch and EBNA2 was analysed. Here, we show that NP9 binds to EBNA2 and negatively affects the EBNA2‐mediated activation of the viral C‐ and LMP2A promoters. In contrast, NP9 did neither interfere in the activation of the HES1 promoter by Notch nor the induction of the viral LMP1 promoter by EBNA2. In an electrophoretic mobility shift analysis, NP9 reduced the binding of EBNA2 to DNA‐bound RBPJκ by about 50%. The down‐regulation of EBNA2‐activity by NP9 might represent a cellular defence mechanism against viral infection or could, alternatively, represent an adaptation of the virus to prevent excessive viral protein production that might otherwise be harmful for the infected cell.