title: Human parainfluenza virus type 2 vector induces dendritic cell maturation without viral RNA replication/transcription.
abstract: The dendritic cell (DC), a most potent antigen-presenting cell, plays a key role in vaccine therapy against infectious diseases and malignant tumors. Although advantages of viral vectors for vaccine therapy have been reported, potential risks for adverse effects prevent them from being licensed for clinical use. Human parainfluenza virus type 2 (hPIV2), one of the members of the Paramyxoviridae family, is a nonsegmented and negative-stranded RNA virus. We have developed a reverse genetics system for the production of infectious hPIV2 lacking the F gene (hPIV2ΔF), wherein various advantages for vaccine therapy exist, such as cytoplasmic replication/transcription, nontransmissible infectivity, and extremely high transduction efficacy in various types of target cells. Here we demonstrate that hPIV2ΔF shows high transduction efficiency in human DCs, while not so high in mouse DCs. In addition, hPIV2ΔF sufficiently induces maturation of both human and murine DCs, and the maturation state of both human and murine DCs is almost equivalent to that induced by lipopolysaccharide. Moreover, alkylating agent β-propiolactone-inactivated hPIV2ΔF (BPL-hPIV2ΔF) elicits DC maturation without viral replication/transcription. These results suggest that hPIV2ΔF may be a useful tool for vaccine therapy as a novel type of paramyxoviral vector, which is single-round infectious vector and has potential adjuvant activity.
authors.affiliation: Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Hara
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fukumura
authors.forename: Junpei
authors.initials: J
authors.lastname: Ohtsuka
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Kawano
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nosaka
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D051379:Mice; D010223:Parainfluenza Virus 2, Human / Q000235:genetics / Q000276:immunology*; D011420:Propiolactone; D060888:Real-Time Polymerase Chain Reaction; D059386:Reverse Genetics / Q000379:methods*; D014161:Transduction, Genetic; D014760:Viral Fusion Proteins / Q000172:deficiency
chemical_list: D017931:DNA Primers; D014760:Viral Fusion Proteins; D011420:Propiolactone