PMID- 19396577 OWN - NLM STAT- MEDLINE DCOM- 20090512 LR - 20220110 IS - 1432-8798 (Electronic) IS - 0304-8608 (Linking) VI - 154 IP - 5 DP - 2009 TI - Characterization of monoclonal antibodies against the nonstructural 5A protein of hepatitis C virus. PG - 843-51 LID - 10.1007/s00705-009-0386-9 [doi] AB - The nonstructural 5A (NS5A) protein of hepatitis C virus (HCV) is a multifunctional protein that leads to pleiotropic responses, in part by regulating cell growth and cellular signaling pathways. Here, we produced monoclonal antibodies (mAbs) directed against the HCV NS5A protein. The N-terminal epitope was mapped to amino acids 60-80 of the NS5A protein, and the epitope in the middle region was mapped to amino acids 221-236. Because these epitopes overlap with binding regions of human vesicle-associated membrane-protein-associated protein (hVAP)-B and TNF-receptor-associated factor 2 (TRAF2), respectively, we investigated these mAbs for their potential capacity to inhibit viral and cellular interactions. We found that NS5A and hVAP-B interaction was abolished by mAb E5D3, and NS5A and TRAF2 interaction was inhibited by mAb C6D4. Since hVAP-B is necessary for HCV replication and TRAF2 is the major transducer in TNF signaling cascades, these data may provide further insights into the mechanisms underlying HCV replication and viral modulation of host signal transduction. FAU - Kang, Sang Min AU - Kang SM AD - National Research Laboratory of Hepatitis C Virus, Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang 431-060, Korea. FAU - Jun, Hyun-Jung AU - Jun HJ FAU - Lim, Yun-Sook AU - Lim YS FAU - Choi, Soo-Ho AU - Choi SH FAU - Hwang, Soon B AU - Hwang SB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090426 PL - Austria TA - Arch Virol JT - Archives of virology JID - 7506870 RN - 0 (Antibodies, Monoclonal) RN - 0 (Epitopes) RN - 0 (TNF Receptor-Associated Factor 2) RN - 0 (VAPB protein, human) RN - 0 (Vesicular Transport Proteins) RN - 0 (Viral Nonstructural Proteins) RN - EC 2.7.7.48 (NS-5 protein, hepatitis C virus) SB - IM MH - Animals MH - Antibodies, Monoclonal/*metabolism MH - Cell Line MH - *Epitope Mapping MH - Epitopes/immunology MH - Female MH - Hepacivirus/*physiology MH - Humans MH - Mice MH - Mice, Inbred BALB C MH - TNF Receptor-Associated Factor 2/metabolism MH - Vesicular Transport Proteins/metabolism MH - Viral Nonstructural Proteins/isolation & purification/*metabolism EDAT- 2009/04/28 09:00 MHDA- 2009/05/13 09:00 CRDT- 2009/04/28 09:00 PHST- 2008/12/01 00:00 [received] PHST- 2009/04/16 00:00 [accepted] PHST- 2009/04/28 09:00 [entrez] PHST- 2009/04/28 09:00 [pubmed] PHST- 2009/05/13 09:00 [medline] AID - 10.1007/s00705-009-0386-9 [doi] PST - ppublish SO - Arch Virol. 2009;154(5):843-51. doi: 10.1007/s00705-009-0386-9. Epub 2009 Apr 26.