Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector
We described earlier a dual-combination anti-HIV type 1 (HIV-1) lentiviral vector (LVsh5/C46) that downregulates CCR5 expression of transduced cells via RNAi and inhibits HIV-1 fusion via cell surface expression of cell membrane-anchored C46 antiviral peptide. This combinatorial approach has two poi...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-01-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253116300221 |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Bryan P Burke Bernard R Levin Jane Zhang Anna Sahakyan Joshua Boyer Maria V Carroll Joanna Camba Colón Naomi Keech Valerie Rezek Gregory Bristol Erica Eggers Ruth Cortado Maureen P Boyd Helen Impey Saki Shimizu Emily L Lowe Gene-Errol E Ringpis Sohn G Kim Dimitrios N Vatakis Louis R Breton Jeffrey S Bartlett Irvin S Y Chen Scott G Kitchen Dong Sung An Geoff P Symonds |
| spellingShingle |
Bryan P Burke Bernard R Levin Jane Zhang Anna Sahakyan Joshua Boyer Maria V Carroll Joanna Camba Colón Naomi Keech Valerie Rezek Gregory Bristol Erica Eggers Ruth Cortado Maureen P Boyd Helen Impey Saki Shimizu Emily L Lowe Gene-Errol E Ringpis Sohn G Kim Dimitrios N Vatakis Louis R Breton Jeffrey S Bartlett Irvin S Y Chen Scott G Kitchen Dong Sung An Geoff P Symonds Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector Molecular Therapy: Nucleic Acids |
| author_facet |
Bryan P Burke Bernard R Levin Jane Zhang Anna Sahakyan Joshua Boyer Maria V Carroll Joanna Camba Colón Naomi Keech Valerie Rezek Gregory Bristol Erica Eggers Ruth Cortado Maureen P Boyd Helen Impey Saki Shimizu Emily L Lowe Gene-Errol E Ringpis Sohn G Kim Dimitrios N Vatakis Louis R Breton Jeffrey S Bartlett Irvin S Y Chen Scott G Kitchen Dong Sung An Geoff P Symonds |
| author_sort |
Bryan P Burke |
| title |
Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector |
| title_short |
Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector |
| title_full |
Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector |
| title_fullStr |
Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector |
| title_full_unstemmed |
Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector |
| title_sort |
engineering cellular resistance to hiv-1 infection in vivo using a dual therapeutic lentiviral vector |
| publisher |
Elsevier |
| series |
Molecular Therapy: Nucleic Acids |
| issn |
2162-2531 |
| publishDate |
2015-01-01 |
| description |
We described earlier a dual-combination anti-HIV type 1 (HIV-1) lentiviral vector (LVsh5/C46) that downregulates CCR5 expression of transduced cells via RNAi and inhibits HIV-1 fusion via cell surface expression of cell membrane-anchored C46 antiviral peptide. This combinatorial approach has two points of inhibition for R5-tropic HIV-1 and is also active against X4-tropic HIV-1. Here, we utilize the humanized bone marrow, liver, thymus (BLT) mouse model to characterize the in vivo efficacy of LVsh5/C46 (Cal-1) vector to engineer cellular resistance to HIV-1 pathogenesis. Human CD34+ hematopoietic stem/progenitor cells (HSPC) either nonmodified or transduced with LVsh5/C46 vector were transplanted to generate control and treatment groups, respectively. Control and experimental groups displayed similar engraftment and multilineage hematopoietic differentiation that included robust CD4+ T-cell development. Splenocytes isolated from the treatment group were resistant to both R5- and X4-tropic HIV-1 during ex vivo challenge experiments. Treatment group animals challenged with R5-tropic HIV-1 displayed significant protection of CD4+ T-cells and reduced viral load within peripheral blood and lymphoid tissues up to 14 weeks postinfection. Gene-marking and transgene expression were confirmed stable at 26 weeks post-transplantation. These data strongly support the use of LVsh5/C46 lentiviral vector in gene and cell therapeutic applications for inhibition of HIV-1 infection. |
| url |
http://www.sciencedirect.com/science/article/pii/S2162253116300221 |
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doaj-3e5b33d836f143b2a0a873b4e98512862020-11-24T22:02:44ZengElsevierMolecular Therapy: Nucleic Acids2162-25312015-01-014C10.1038/mtna.2015.10Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral VectorBryan P Burke0Bernard R Levin1Jane Zhang2Anna Sahakyan3Joshua Boyer4Maria V Carroll5Joanna Camba Colón6Naomi Keech7Valerie Rezek8Gregory Bristol9Erica Eggers10Ruth Cortado11Maureen P Boyd12Helen Impey13Saki Shimizu14Emily L Lowe15Gene-Errol E Ringpis16Sohn G Kim17Dimitrios N Vatakis18Louis R Breton19Jeffrey S Bartlett20Irvin S Y Chen21Scott G Kitchen22Dong Sung An23Geoff P Symonds24Calimmune, Inc., Los Angeles, California, USADivision of Hematology–Oncology and the UCLA Center for AIDS Research (CFAR), David Geffen School of Medicine at UCLA, Los Angeles, California, USACalimmune, Inc., Los Angeles, California, USASchool of Nursing at UCLA, UCLA AIDS Institute, Los Angeles, California, USASchool of Nursing at UCLA, UCLA AIDS Institute, Los Angeles, California, USACalimmune, Inc., Los Angeles, California, USACalimmune, Inc., Los Angeles, California, USACalimmune, Inc., Los Angeles, California, USADivision of Hematology–Oncology and the UCLA Center for AIDS Research (CFAR), David Geffen School of Medicine at UCLA, Los Angeles, California, USADivision of Hematology–Oncology and the UCLA Center for AIDS Research (CFAR), David Geffen School of Medicine at UCLA, Los Angeles, California, USASchool of Nursing at UCLA, UCLA AIDS Institute, Los Angeles, California, USASchool of Nursing at UCLA, UCLA AIDS Institute, Los Angeles, California, USACalimmune, Inc., Los Angeles, California, USACalimmune, Inc., Los Angeles, California, USASchool of Nursing at UCLA, UCLA AIDS Institute, Los Angeles, California, USASchool of Nursing at UCLA, UCLA AIDS Institute, Los Angeles, California, USACalimmune, Inc., Los Angeles, California, USADivision of Hematology–Oncology and the UCLA Center for AIDS Research (CFAR), David Geffen School of Medicine at UCLA, Los Angeles, California, USADivision of Hematology–Oncology and the UCLA Center for AIDS Research (CFAR), David Geffen School of Medicine at UCLA, Los Angeles, California, USACalimmune, Inc., Los Angeles, California, USACalimmune, Inc., Los Angeles, California, USADepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, USADivision of Hematology–Oncology and the UCLA Center for AIDS Research (CFAR), David Geffen School of Medicine at UCLA, Los Angeles, California, USASchool of Nursing at UCLA, UCLA AIDS Institute, Los Angeles, California, USACalimmune, Inc., Los Angeles, California, USAWe described earlier a dual-combination anti-HIV type 1 (HIV-1) lentiviral vector (LVsh5/C46) that downregulates CCR5 expression of transduced cells via RNAi and inhibits HIV-1 fusion via cell surface expression of cell membrane-anchored C46 antiviral peptide. This combinatorial approach has two points of inhibition for R5-tropic HIV-1 and is also active against X4-tropic HIV-1. Here, we utilize the humanized bone marrow, liver, thymus (BLT) mouse model to characterize the in vivo efficacy of LVsh5/C46 (Cal-1) vector to engineer cellular resistance to HIV-1 pathogenesis. Human CD34+ hematopoietic stem/progenitor cells (HSPC) either nonmodified or transduced with LVsh5/C46 vector were transplanted to generate control and treatment groups, respectively. Control and experimental groups displayed similar engraftment and multilineage hematopoietic differentiation that included robust CD4+ T-cell development. Splenocytes isolated from the treatment group were resistant to both R5- and X4-tropic HIV-1 during ex vivo challenge experiments. Treatment group animals challenged with R5-tropic HIV-1 displayed significant protection of CD4+ T-cells and reduced viral load within peripheral blood and lymphoid tissues up to 14 weeks postinfection. Gene-marking and transgene expression were confirmed stable at 26 weeks post-transplantation. These data strongly support the use of LVsh5/C46 lentiviral vector in gene and cell therapeutic applications for inhibition of HIV-1 infection.http://www.sciencedirect.com/science/article/pii/S2162253116300221 |