title: Novel gene therapy viral vector using non-oncogenic lymphotropic herpesvirus.
abstract: Despite the use of retroviral vectors, efficiently introducing target genes into immunocytes such as T cells is difficult. In addition, retroviral vectors carry risks associated with the oncogenicity of the native virus and the potential for introducing malignancy in recipients due to genetic carryover from immortalized cells used during vector production. To address these issues, we have established a new virus vector that is based on human herpesvirus 6 (HHV-6), a non-oncogenic lymphotropic herpesvirus that infects CD4(+) T cells, macrophages, and dendritic cells. In the present study, we have altered the cell specificity of the resulting recombinant HHV-6 by knocking out the U2-U8 genes. The resulting virus proliferated only in activated cord blood cells and not in peripheral blood cells. Umbilical cord blood cells produced replication-defective recombinant virus in sufficiently high titer to omit the use of immortalized cells during vector production. HHV-6 vectors led to high rates (>90%) of gene transduction in both CD4(+) and CD8(+) T cells. These viruses showed low-level replication of viral DNA that supported greater expression of the induced genes than that of other methods but that was insufficient to support the production of replication-competent virus. Furthermore, HHV-6 vectors containing short hairpin RNAs against CD4 and HIV Gag remarkably inhibited the production of these proteins and HIV particles. Here we demonstrate the utility of HHV-6 as a new non-carcinogenic viral vector for immunologic diseases and immunotherapy.
authors: Department of Virology, The Jikei University School of Medicine, Tokyo, Japan.
authors: Akihiro
authors: A
authors: Shimizu
authors: Nobuyuki
authors: N
authors: Kobayashi
authors: Kazuya
authors: K
authors: Shimada
authors: Kuniaki
authors: K
authors: Oura
authors: Tadao
authors: T
authors: Tanaka
authors: Aikou
authors: A
authors: Okamoto
authors: Kazuhiro
authors: K
authors: Kondo
mesh_terms: D003588:Cytopathogenic Effect, Viral; D015870:Gene Expression; D005786:Gene Expression Regulation; D023061:Gene Order; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D016679:Genome, Viral; D015654:Herpesvirus 6, Human / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D008214:Lymphocytes / Q000378:metabolism / Q000821:virology; D034622:RNA Interference; D019076:Transgenes; D056189:Viral Tropism; D014779:Virus Replication
chemical_list: D007372:Interferons