title: HCV peptide (C5A), an amphipathic α-helical peptide of hepatitis virus C, is an activator of N-formyl peptide receptor in human phagocytes.
abstract: The hepatitis C virus (HCV) nonstructural 5A, a phosphorylated zinc metalloprotein, is an essential component of the HCV replication complex. An amphipathic α-helical peptide (HCV peptide [C5A]) derived from nonstructural 5A membrane anchor domain possesses potent anti-HCV and anti-HIV activity in vitro. In this study, we aimed to investigate the potential of HCV peptide (C5A) to regulate host immune responses. The capacity of HCV peptide (C5A) in vitro to induce migration and calcium mobilization of human phagocytes and chemoattractant receptor-transfected cells was investigated. The recruitment of phagocytes in vivo induced by HCV peptide (C5A) and its adjuvant activity were examined. The results revealed that HCV peptide (C5A) was a chemoattractant and activator of human phagocytic leukocytes by using a G-protein coupled receptor, namely formyl peptide receptor. In mice, HCV peptide (C5A) induced massive phagocyte infiltration after injection in the air pouch or the s.c. region. HCV peptide (C5A) also acted as an immune adjuvant by enhancing specific T cell responses to Ag challenge in mice. Our results suggest that HCV peptide (C5A) derived from HCV regulates innate and adaptive immunity in the host by activating the formyl peptide receptor.
authors.affiliation: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China;
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.forename: Dan
authors.initials: D
authors.lastname: Fang
authors.forename: Xinwei
authors.initials: X
authors.lastname: Hou
authors.forename: Yingying
authors.initials: Y
authors.lastname: Le
authors.forename: Jiazhu
authors.initials: J
authors.lastname: Fang
authors.forename: Feng
authors.initials: F
authors.lastname: Wen
authors.forename: Wanghua
authors.initials: W
authors.lastname: Gong
authors.forename: Keqiang
authors.initials: K
authors.lastname: Chen
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
authors.forename: Shao Bo
authors.initials: SB
authors.lastname: Su
mesh_terms: D056704:Adaptive Immunity; D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology*; D010586:Phagocytes / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D044042:Receptors, Formyl Peptide / Q000378:metabolism* / Q000502:physiology; D044067:Receptors, Lipoxin / Q000378:metabolism* / Q000502:physiology; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000502:physiology*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D008565:Membrane Proteins; D010446:Peptide Fragments; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D017361:Viral Nonstructural Proteins; C105101:FPR2 protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase