| 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
|
| リソース情報 |
| ヒト・動物細胞 |
BHK-21(RCB1423) |
