HIV-1 Latency: An Update of Molecular Mechanisms and Therapeutic Strategies

被引:51
作者
Battistini, Angela [1 ]
Sgarbanti, Marco [1 ]
机构
[1] Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, I-00161 Rome, Italy
来源
VIRUSES-BASEL | 2014年 / 6卷 / 04期
关键词
mechanisms of latency; reactivating compounds; latency; immune therapy; HIV; HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; HISTONE DEACETYLASE INHIBITORS; ACTIVE ANTIRETROVIRAL THERAPY; RETROVIRUSES HTLV-III; LONG TERMINAL REPEAT; BET BROMODOMAIN INHIBITION; CXCR4 CHEMOKINE RECEPTOR; B P-TEFB; IMMUNE-ACTIVATION;
D O I
10.3390/v6041715
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The major obstacle towards HIV-1 eradication is the life-long persistence of the virus in reservoirs of latently infected cells. In these cells the proviral DNA is integrated in the host's genome but it does not actively replicate, becoming invisible to the host immune system and unaffected by existing antiviral drugs. Rebound of viremia and recovery of systemic infection that follows interruption of therapy, necessitates life-long treatments with problems of compliance, toxicity, and untenable costs, especially in developing countries where the infection hits worst. Extensive research efforts have led to the proposal and preliminary testing of several anti-latency compounds, however, overall, eradication strategies have had, so far, limited clinical success while posing several risks for patients. This review will briefly summarize the more recent advances in the elucidation of mechanisms that regulates the establishment/maintenance of latency and therapeutic strategies currently under evaluation in order to eradicate HIV persistence.
引用
收藏
页码:1715 / 1758
页数:44
相关论文
共 287 条
[1]  
Abrams D, 2009, NEW ENGL J MED, V361, P1548, DOI 10.1056/NEJMoa0903175
[2]   Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation [J].
Allers, Kristina ;
Huetter, Gero ;
Hofmann, Joerg ;
Loddenkemper, Christoph ;
Rieger, Kathrin ;
Thiel, Eckhard ;
Schneider, Thomas .
BLOOD, 2011, 117 (10) :2791-2799
[3]   Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover [J].
Almeida, Jorge R. ;
Price, David A. ;
Papagno, Laura ;
Arkoub, Zaina Ait ;
Sauce, Delphine ;
Bornstein, Ethan ;
Asher, Tedi E. ;
Samri, Assia ;
Schnuriger, Aurelie ;
Theodorou, Ioannis ;
Costagliola, Dominique ;
Rouzioux, Christine ;
Agut, Henri ;
Marcelin, Anne-Genevieve ;
Douek, Daniel ;
Autran, Brigitte ;
Appay, Victor .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (10) :2473-2485
[4]  
ANDREEFF M, 1992, BLOOD, V80, P2604
[5]   Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy [J].
Archin, N. M. ;
Liberty, A. L. ;
Kashuba, A. D. ;
Choudhary, S. K. ;
Kuruc, J. D. ;
Crooks, A. M. ;
Parker, D. C. ;
Anderson, E. M. ;
Kearney, M. F. ;
Strain, M. C. ;
Richman, D. D. ;
Hudgens, M. G. ;
Bosch, R. J. ;
Coffin, J. M. ;
Eron, J. J. ;
Hazuda, D. J. ;
Margolis, D. M. .
NATURE, 2012, 487 (7408) :482-U1650
[6]   Expression of Latent HIV Induced by the Potent HDAC Inhibitor Suberoylanilide Hydroxamic Acid [J].
Archin, Nancie M. ;
Espeseth, Amy ;
Parker, Daniel ;
Cheema, Manzoor ;
Hazuda, Daria ;
Margolis, David M. .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 2009, 25 (02) :207-212
[7]   Bryostatin-1, a Naturally Occurring Antineoplastic Agent, Acts as a Toll-like Receptor 4 (TLR-4) Ligand and Induces Unique Cytokines and Chemokines in Dendritic Cells [J].
Ariza, Maria Eugenia ;
Ramakrishnan, Rupal ;
Singh, Narendra P. ;
Chauhan, Ashok ;
Nagarkatti, Prakash S. ;
Nagarkatti, Mitzi .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (01) :24-34
[8]  
Autran Brigitte, 2004, Expert Rev Vaccines, V3, pS169, DOI 10.1586/14760584.3.4.S169
[9]   Immune control of HIV-1 reservoirs [J].
Autran, Brigitte ;
Descours, Benjamin ;
Bacchus, Charline .
CURRENT OPINION IN HIV AND AIDS, 2013, 8 (03) :204-210
[10]   Pegylated Interferon Alfa-2a Monotherapy Results in Suppression of HIV Type 1 Replication and Decreased Cell-Associated HIV DNA Integration [J].
Azzoni, Livio ;
Foulkes, Andrea S. ;
Papasavvas, Emmanouil ;
Mexas, Angela M. ;
Lynn, Kenneth M. ;
Mounzer, Karam ;
Tebas, Pablo ;
Jacobson, Jeffrey M. ;
Frank, Ian ;
Busch, Michael P. ;
Deeks, Steven G. ;
Carrington, Mary ;
O'Doherty, Una ;
Kostman, Jay ;
Montaner, Luis J. .
JOURNAL OF INFECTIOUS DISEASES, 2013, 207 (02) :213-222