title: Viral suppression function of intracellular antibody against C-terminal domain of rabies virus phosphoprotein.
abstract: Rabies virus (RV) causes a fatal disease in both human and animals. The disease can be prevented by post-exposure prophylaxis in individuals exposed to RV. However, the neutralization effect is limited after the virus enters into the host cells. So, it is important to identify new targets for rabies therapy. In this study, a human antibody RV1A2 specific to RV phosphoprotein (RV-P) was generated from a human naïve immune antibody library. The antibody recognized all forms of the phosphoproteins including the full length (P1) and short length of the P proteins (P2, P3, P4, and P5). The epitope mapping and the molecular docking of antigen-antibody complex showed that the antibody targets at a conserved epitope of 'VLGWV' ranging from amino acid (aa) 262 to 266 at C-terminal domain of the P protein, which locates at a hydrophobic pocket region in the C-terminal of the RV-P. The aa W265 within the epitope is on the flat surface of the domain, suggesting that it may be a critical amino acid for the functions of the P protein. Our results further showed that intracellular antibody RV1A2 which targets at the C-terminal domain of the P protein could effectively inhibit RV propagation 2-4 days post infection. These results suggest that the conserved C-terminal domain may be used as a new target for drug discovery, which highlights an intracellular inhibition of RV propagation and provides a potential novel way to treat RV infection.
authors.affiliation: Key Laboratory for Medical Virology, NHFPC, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory for Medical Virology, NHFPC, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Sun
authors.affiliation: Key Laboratory for Medical Virology, NHFPC, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Yu
authors.affiliation: Key Laboratory for Medical Virology, NHFPC, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.
authors.forename: Aqian
authors.initials: A
authors.lastname: Li
authors.affiliation: Key Laboratory for Medical Virology, NHFPC, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory for Medical Virology, NHFPC, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Key Laboratory for Medical Virology, NHFPC, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Li
authors.affiliation: Key Laboratory for Medical Virology, NHFPC, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China mifangl@vip.sina.com.
authors.forename: Mifang
authors.initials: M
authors.lastname: Liang
mesh_terms: D000914:Antibodies, Viral / Q000008:administration & dosage / Q000276:immunology*; D001665:Binding Sites; D057809:HEK293 Cells; D006801:Humans; D010750:Phosphoproteins / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011820:Rabies virus / Q000737:chemistry* / Q000187:drug effects / Q000276:immunology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
chemical_list: D000914:Antibodies, Viral; D010750:Phosphoproteins
keywords: human fab library; intracellular antibody (intrabody); rabies virus (RV); rabies virus phosphoprotein (RV-P); single-chain variable fragment (scFv)