| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Shepherd, Nicole Yang, Kai Desai, Mona Byrd, Daniel Gupta, Samir Gao, Jimin Sun, Yongtao Yu, Qigui Hu, Ningjie Amet, Tohti Lan, Jie |
| Description |
Author Affiliation: Lan J ( Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202); Yang K ( Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202); Byrd D ( Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202); Hu N ( Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, Wenzhou Medical College, Wenzhou 325035, China); Amet T ( Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202); Shepherd N ( Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202); Desai M ( Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202); Gao J ( Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, Wenzhou Medical College, Wenzhou 325035, China); Gupta S ( Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202); Sun Y ( Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.); Yu Q ( Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202) |
| Abstract |
Latently HIV-1-infected cells are recognized as the last barrier toward viral eradication and cure. To purge these cells, we combined a provirus stimulant with a blocker of human CD59, a key member of the regulators of complement activation, to trigger Ab-dependent complement-mediated lysis. Provirus stimulants including prostratin and histone deacetylase inhibitors such as romidepsin and suberoylanilide hydroxamic acid activated proviruses in the latently HIV-1-infected T cell line ACH-2 as virion production and viral protein expression on the cell surface were induced. Romidepsin was the most attractive provirus stimulant as it effectively activated proviruses at nanomolar concentrations that can be achieved clinically. Antiretroviral drugs including two protease inhibitors (atazanavir and darunavir) and an RT inhibitor (emtricitabine) did not affect the activity of provirus stimulants in the activation of proviruses. However, saquinavir (a protease inhibitor) markedly suppressed virus production, although it did not affect the percentage of cells expressing viral Env on the cell surface. Provirus-activated ACH-2 cells expressed HIV-1 Env that colocalized with CD59 in lipid rafts on the cell surface, facilitating direct interaction between them. Blockage of CD59 rendered provirus-activated ACH-2 cells and primary human CD4(+) T cells that were latently infected with HIV-1 sensitive to Ab-dependent complement-mediated lysis by anti-HIV-1 polyclonal Abs or plasma from HIV-1-infected patients. Therefore, a combination of provirus stimulants with regulators of complement activation blockers represents a novel approach to eliminate HIV-1. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1303030 |
| Journal |
The Journal of Immunology |
| Issue Number |
7 |
| Volume Number |
193 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-10-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Antibody-dependent Cell Cytotoxicity Antigens, Cd59 Immunology Complement Activation Complement System Proteins Hiv Antibodies Hiv Infections Hiv-1 Proviruses Adolescent Anti-hiv Agents Administration & Dosage Cell Line Hiv Envelope Protein Gp160 Drug Therapy Pathology Clinical Trial Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
