Abstract:
:Cessation of highly active antiretroviral therapy (HAART) in HIV-infected individual leads to a rebound of viral replication due to reactivation of a viral reservoir composed largely of latently infected memory CD4(+) T cells. Efforts to deplete this reservoir have focused on reactivation of transcriptionally silent latent proviruses. HIV provirus transcription depends critically on the positive transcription elongation factor b (P-TEFb), whose core components are cyclin-dependent kinase 9 (CDK9) and cyclin T1. In resting CD4(+) cells, the functional levels of P-TEFb are extremely low. Cellular activation upregulates cyclin T1 protein levels and CDK9 T-loop (T186) phosphorylation. The broad-spectrum histone deacetylase inhibitors (HDACis) vorinostat and panobinostat have been shown to reactivate latent virus in vivo in HAART-treated individuals. In this study, we have found that vorinostat and panobinostat activate P-TEFb in resting primary CD4(+) T cells through induction of CDK9 T-loop phosphorylation. In contrast, tacedinaline and romidepsin, HDAC 1 and 2 inhibitors, were unable to activate CDK9 T-loop phosphorylation. We used a CCL19 primary CD4(+) T-cell model HIV latency to assess the correlation between induction of CDK9 T-loop phosphorylation and reactivation of latent HIV virus by HDACis. Vorinostat and panobinostat treatment of cells harboring latent HIV increased CDK9 T-loop phosphorylation and reactivation of latent virus, whereas tacedinaline and romidepsin failed to induce T-loop phosphorylation or reactivate latent virus. We conclude that the ability of vorinostat and panobinostat to induce latent HIV is, in part, likely due to the ability of the broad-spectrum HDACis to upregulate P-TEFb through increased CDK9 T-loop phosphorylation.
journal_name
AIDS Res Hum Retrovirusesjournal_title
AIDS research and human retrovirusesauthors
Jamaluddin MS,Hu PW,Jan Y,Siwak EB,Rice APdoi
10.1089/AID.2015.0347subject
Has Abstractpub_date
2016-02-01 00:00:00pages
169-73issue
2eissn
0889-2229issn
1931-8405journal_volume
32pub_type
杂志文章abstract::Population genotyping (PG) can underestimate resistance if resistance-containing low abundance variants go undetected. PG and clonal analysis (CA) results were compared in virologic failures (VFs) from a 48-week clinical trial that evaluated once-daily fosamprenavir/ritonavir (FPV/r) 1400 mg/100 mg or atazanavir/riton...
journal_title:AIDS research and human retroviruses
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1089/aid.2009.0189
更新日期:2010-04-01 00:00:00
abstract::We aimed to determine the prevalence of a prolonged QTc interval in HIV-infected patients and its related factors through an observational study of a cohort of asymptomatic HIV-infected outpatients. All patients underwent a standard 12-lead electrocardiogram and a transthoracic echocardiogram. Prolonged QTc was consid...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2013.0061
更新日期:2013-09-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1995.11.171
更新日期:1995-01-01 00:00:00
abstract::We have determined that polymeric IgA in saliva of HIV-1-uninfected individuals binds in varying degrees to components of culture supernatants containing HIV-1 recombinant proteins when ELISA is used for the determination. This finding did not extend to salivary IgG antibodies. Further, such problems were not encounte...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922200309016
更新日期:2000-04-10 00:00:00
abstract::Il28B single nucleotide polymorphisms were found to influence interferon λ expression, resulting in changes in hepatitis C virus (HCV)-RNA serum levels as well as the HIV-RNA set point prior to combined antiretroviral therapy (cART). To date, there is limited information on the influence of this polymorphism on surviv...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2011.0354
更新日期:2012-12-01 00:00:00
abstract::Inhibitory factors to human immunodeficiency virus type 1 (HIV-1) in saliva may be responsible for the infrequent isolation of virus from saliva and also may account for the marked infrequency of salivary and/or oral transmission of HIV-1. Incubation of HIV-1 with human saliva followed by addition of the mixture to su...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1990.6.1425
更新日期:1990-12-01 00:00:00
abstract::Interleukin-15 (IL-15) enhances the effector mechanisms of anti-HIV immune responses and thus is considered a potential adjuvant of HIV-1 vaccine. However, there are a lack of data concerning the relationships between IL-15 expression and regulation in HIV-1-infected patients and the course of disease progression. We ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2010.0317
更新日期:2012-07-01 00:00:00
abstract::Murine monoclonal antibodies (MAbs) raised against a recombinant nef protein fragment of human immunodeficiency virus type 1 (HIV-1) strain BH10 were characterized by an epitope mapping system using overlapping decapeptides. Four different immunogenic regions were identified. Ten human HIV-1-positive sera were tested ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1991.7.37
更新日期:1991-01-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922204773004842
更新日期:2004-02-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2011.0264
更新日期:2012-08-01 00:00:00
abstract::We sought to determine the pattern of resistance-associated mutations (RAMs) among HIV-1-infected children failing first-line antiretroviral therapy (ART) and ascertain their response to second-line regimens in 48 weeks of follow-up. The design involved a cohort study within an HIV care program. We studied records of ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2012.0283
更新日期:2013-03-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,多中心研究
doi:10.1089/AID.2016.0144
更新日期:2017-03-01 00:00:00
abstract::In order to investigate how human immunodeficiency virus (HIV) gains entry to the placenta, we have performed in vitro experiments in which highly purified trophoblast cells isolated from term human placentas were examined for their susceptibility to HIV infection. Trophoblast cells were exposed to cell-free HIV-1 for...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1991.7.735
更新日期:1991-09-01 00:00:00
abstract::Japan is one of the highest endemic areas of the world for human T cell leukemia-lymphoma virus type I (HTLV-I). To gain new insight as to the origin of this virus in Japan and especially in the southern islands of the archipelago, we investigated the long terminal repeat (LTR) of 67 newly isolated HTLV-I proviral DNA...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1994.10.1557
更新日期:1994-11-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2013.0289
更新日期:2014-07-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1995.11.335
更新日期:1995-03-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922200309205
更新日期:2000-03-01 00:00:00
abstract::The U.S. military represents a unique population within the human immunodeficiency virus 1 (HIV-1) pandemic. The last comprehensive study of HIV-1 in members of the U.S. Navy and Marine Corps (Sea Services) was completed in 2000, before large-scale combat operations were taking place. Here, we present molecular charac...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2013.0087
更新日期:2013-10-01 00:00:00
abstract::The molecular epidemiology of HIV-1 in Argentina is more complex than was previously appreciated. One circulating recombinant form, CRF12_BF, and many related BF recombinant forms predominate in the capital city, Buenos Aires. This study of HIV-1 subtypes acquired perinatally between 1984 and 2000 has permitted, for t...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922202317406619
更新日期:2002-05-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1991.7.923
更新日期:1991-11-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922299311330
更新日期:1999-03-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2009.0179
更新日期:2010-01-01 00:00:00
abstract::An increasing number of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) all over the world has necessitated being vigilant about new recombinants. Since the first report of a recombinant virus with an A1/C mosaic in 1998 more and more B/C and A/C recombinant viruses are being reported from Ind...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2013.0150
更新日期:2013-09-01 00:00:00
abstract::In an attempt to develop an immunization strategy to induce mucosal and circulatory antibodies against SIV antigens, we have investigated the potential of attenuated recombinant vaccinia virus to deliver SIV antigens (gp160 of SIVmac239) to mucosal surfaces of mice. After systemic or mucosal (intragastric, intranasal,...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922299309982
更新日期:1999-11-01 00:00:00
abstract::Epidemiological studies strongly suggest that a newly discovered herpesvirus, Kaposi's sarcoma associated-herpesvirus (KSHV/HHV8), is the likely infectious cause of Kaposi's sarcoma (KS). Identification of this agent suggests the possibility that existing anti-herpesvirus chemotherapeutics have activity against KSHV. ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1997.13.1229
更新日期:1997-09-20 00:00:00
abstract::A murine monoclonal antibody (MoAb), VAK 4, has been known to specifically react with a major core protein (p24) as well as with its precursor (p55-57) and intermediate precursor (p40) of human immunodeficiency virus strain IIIB (HTLV-IIIB). Radioimmunoprecipitation assays revealed that VAK 4 MoAb precipitated a major...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1988.4.409
更新日期:1988-12-01 00:00:00
abstract::Because mucosal inflammation contributes to colorectal carcinogenesis, we studied the impact of intestinal infections on risk of this malignancy among people with AIDS (PWA). Using the population-based HIV/AIDS Cancer Match, which includes approximately half of all PWA in the United States, the cancer registries ascer...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,多中心研究
doi:10.1089/AID.2011.0185
更新日期:2012-09-01 00:00:00
abstract::In this report we have highlighted only a few examples of the extensive efforts underway to better understand the process of HIV pathogenesis, to develop new therapeutic agents to inhibit virus replication, and to identify strategies to restore damage done to the immune system during HIV disease progression. It is exp...
journal_title:AIDS research and human retroviruses
pub_type:
doi:10.1089/aid.1996.12.859
更新日期:1996-07-01 00:00:00
abstract::Transmission of HIV-1 and drug resistance continue to occur at a considerable level in Italy, influenced mainly by changes in modality of infection. However, the long period of infectivity makes difficult the interpretation of epidemiological networks, based on epidemiological data only. We studied 510 naive HIV-1-inf...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2011.0245
更新日期:2012-08-01 00:00:00