論文 - 詳細
| RRC ID | 52026 |
|---|---|
| 著者 | Okuma K, Fukagawa K, Kohma T, Takahama Y, Hamaguchi Y, Ito M, Tanaka Y, Buonocore L, Rose JK, Hamaguchi I. |
| タイトル | A recombinant vesicular stomatitis virus encoding CCR5-tropic HIV-1 receptors targets HIV-1-infected cells and controls HIV-1 infection. |
| ジャーナル | Microbes Infect |
| Abstract |
Anti-retroviral therapy is useful to treat human immunodeficiency virus type 1 (HIV-1)-infected individuals, but has some major problems, such as the generation of multidrug-resistant viruses. To develop a novel supplemental or alternative therapeutic for CCR5-tropic (R5) HIV-1 infection, we generated a recombinant vesicular stomatitis virus (rVSV) in which the gene encoding its envelope glycoprotein (G) was replaced with the genes encoding R5 HIV-1 receptors (human CD4 and CCR5), designated VSVΔG-CC5. Our present data demonstrate that this rVSV specifically infects cells that are transiently expressing R5 HIV-1 envelope glycoproteins, but does not infect those expressing CXCR4-tropic HIV-1 envelope glycoproteins. Notably, after a CD4+CCR5+ T cell line or primary cells initially infected with R5 HIV-1 were inoculated with G-complemented VSVΔG-CC5, the rVSV significantly reduced the number of HIV-1-infected cells, probably through direct targeting of the rVSV and VSV-mediated cytolysis and/or through syncytium formation- or cell-cell fusion-dependent killing, and markedly inhibited HIV-1 production. Furthermore, G-complemented VSVΔG-CC5 also efficiently inhibited HIV-1 infection in R5 HIV-1-infected humanized immunodeficient mice. Taken together, our findings indicate that a cytolytic rVSV that targets and eliminates R5 HIV-1-infected cells potentially has therapeutic value for controlling R5 HIV-1 infection. |
| 巻・号 | 19(4-5) |
| ページ | 277-287 |
| 公開日 | 2017-1-1 |
| DOI | 10.1016/j.micinf.2016.12.004 |
| PII | S1286-4579(16)30212-X |
| PMID | 28025070 |
| MeSH | Animals Antiviral Agents / pharmacology CD4 Antigens / genetics* CD4 Antigens / metabolism CD4-Positive T-Lymphocytes / metabolism CD4-Positive T-Lymphocytes / virology Cell Line Cricetinae HEK293 Cells HIV Infections / prevention & control* HIV Infections / virology HIV-1 / genetics Humans Mice Mice, Inbred BALB C Mice, Nude Oncolytic Virotherapy / methods* Receptors, CCR5 / genetics* Receptors, CCR5 / metabolism Receptors, CXCR4 / metabolism Vesiculovirus / genetics* Viral Envelope Proteins / genetics* Viral Load Virus Replication / genetics* |
| IF | 2.373 |
| 引用数 | 2 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 19 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | BHK-21(RCB1423) |