Micro RNA Targets in HIV Latency: Insights into Novel Layers of Latency Control.

Abstract:

:Despite the considerable progress that has been made in identifying cellular factors and pathways that contribute to establishment and maintenance of the latent HIV reservoir, it remains the major obstacle to eradicating this virus. Most recently, noncoding genes have been implicated in regulation of HIV expression. In this study, small RNA sequencing was used to profile expression of microRNAs (miRNAs) in a primary CD4+ T cell in vitro model of HIV latency. Previously, we have shown that protein-coding genes dysregulated in this model were enriched for the p53 signaling pathway, which was confirmed experimentally. We further found a link between p53 signaling and dysregulated long noncoding RNAs. In this study, we hypothesized that miRNAs may provide an additional level of regulation of the p53 signaling pathway during HIV latency. Twenty-six miRNAs were identified to be dysregulated in our latency model. A subset of these miRNAs was validated by real-time quantitative polymerase chain reaction. Predicted messenger RNA (mRNA) targets and cellular pathways enriched for mRNA targets were identified using several analytical methods. Our analyses showed that many protein-coding genes and pathways targeted by dysregulated miRNAs have relevance to regulation of HIV expression or establishment of HIV latency. The p53 signaling pathway was found among pathways that were targeted by dysregulated miRNAs at a greater level than expected by chance. This study provides a mechanistic insight into regulation of the p53 pathway through miRNAs that may contribute to the establishment of latency.

authors

Heinson AI,Woo J,Mukim A,White CH,Moesker B,Bosque A,Spina CA,Woelk CH,Macarthur BD,Beliakova-Bethell N

doi

10.1089/AID.2020.0150

subject

Has Abstract

pub_date

2020-11-10 00:00:00

eissn

0889-2229

issn

1931-8405

pub_type

杂志文章
  • Genetic characterization of HIV before widespread testing of HIV vaccine candidates at a clinical trial site in Pretoria, South Africa.

    abstract::We studied 123 samples from adult chronic HIV patients initiating HAART from various centers around a newly established clinical trial site in Pretoria. Each sample was sequenced in at least one structural gene (pol, gag, and env) or functional gene (vif, vpr, and vpu). A subset of 25 samples was subjected to near ful...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章,多中心研究

    doi:10.1089/AID.2011.0285

    authors: Musyoki A,Mothapo K,Rakgole J,Lukhwareni A,Bessong P,Selabe G,Bredell H,Williamson C,Mphahlele MJ

    更新日期:2012-09-01 00:00:00

  • Targeting of a CD8 T cell env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure.

    abstract::In HIV-infected persons, certain HLA class I alleles are associated with effective control of viremia, while others are associated with rapid disease progression. Among the most divergent clinical outcomes are the relatively good prognosis in HLA-B*5801 expressing persons and poor prognosis with HLA-B*5802. These two ...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2007.0124

    authors: Ngumbela KC,Day CL,Mncube Z,Nair K,Ramduth D,Thobakgale C,Moodley E,Reddy S,de Pierres C,Mkhwanazi N,Bishop K,van der Stok M,Ismail N,Honeyborne I,Crawford H,Kavanagh DG,Rousseau C,Nickle D,Mullins J,Heckerman D,K

    更新日期:2008-01-01 00:00:00

  • Lymphocyte homeostasis in HIV-infected northern Thais.

    abstract::Cross-sectional laboratory data were used to model the patterns of total lymphocyte count and lymphocyte subpopulation counts among persons with chronic HIV-1 subtype E (CRF01_AE) infection during the 6.5 years preceding death. The data cover 331 HIV-infected decedents from a heterosexual HIV transmission study of 590...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/0889222041217491

    authors: Kingkeow D,Heilig CM,Costello C,Sennun S,Suriyanon V,Rungruengthanakit K,Taejaroenkul S,Nelson KE,Duerr A

    更新日期:2004-06-01 00:00:00

  • Lipid rafts and HIV pathogenesis: virion-associated cholesterol is required for fusion and infection of susceptible cells.

    abstract::We have shown that HIV budding occurs at cholesterol-rich membrane microdomains called lipid rafts (Nguyen and Hildreth, J Virol 2000;74:3264-3272). This observation prompted us to examine the role in HIV entry of cholesterol in the membrane of cells. We recently reported that host cell cholesterol is required for HIV...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/088922203322280900

    authors: Liao Z,Graham DR,Hildreth JE

    更新日期:2003-08-01 00:00:00

  • Membrane-interactive phospholipids inhibit HIV type 1-induced cell fusion and surface gp160/gp120 binding to monoclonal antibody.

    abstract::Membrane-interactive phospholipids (PLs), previously evaluated for activity against HIV-1 in vitro, are known to affect late steps in viral replication. Studies were done to determine the effects of PL analogs on post-translational processing of HIV-1 proteins, binding of viral surface gp160/gp120 to CD4 receptor, and...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1995.11.705

    authors: Krugner-Higby L,Goff D,Edwards T,Iyer N,Neufeld J,Kute T,Morris-Natschke S,Ishaq K,Piantadosi C,Kucera LS

    更新日期:1995-06-01 00:00:00

  • Progressive impairment of monocytic function in HIV-1-infected human macrophage hybridomas.

    abstract::Using human macrophage hybridomas infected with HIV-1, we investigated monocyte function over a 5-week period after HIV-1 infection. Two clones, 63 and 30, were infected with HIV-1IIIB. Infection was documented by RT activity (15 x 10(6) cpm/ml), intracytoplasmic staining with an anti-p24 antibody, in situ hybridizati...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1993.9.657

    authors: Sperber K,Hamrang G,Louie MJ,Kalb T,Banerjee R,Choi HS,Paronetto F,Mayer L

    更新日期:1993-07-01 00:00:00

  • Elimination of human T cell leukemia virus type-1-infected cells by neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies against human t cell leukemia virus type-1 envelope gp46.

    abstract::Human T cell leukemia virus type-1 (HTLV-1) is prevalent worldwide with foci of high prevalence. However, to date no effective vaccine or drug against HTLV-1 infection has been developed. In efforts to define the role of antibodies in the control of HTLV-1 infection, we capitalized on the use of our previously defined...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2013.0214

    authors: Tanaka Y,Takahashi Y,Tanaka R,Kodama A,Fujii H,Hasegawa A,Kannagi M,Ansari AA,Saito M

    更新日期:2014-06-01 00:00:00

  • Activation and regulation of interferon regulatory factor 4 in HTLV type 1-infected T lymphocytes.

    abstract::The human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL), an aggressive and fatal leukemia of CD4(+) T lymphocytes, and is also associated with a neurological demyelinating disease, tropical spastic paraparesis. The oncogenic potential of HTLV-1 resides in the 353-aa, 40-kD...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/08892220050193047

    authors: Sharma S,Mamane Y,Grandvaux N,Bartlett J,Petropoulos L,Lin R,Hiscott J

    更新日期:2000-11-01 00:00:00

  • Sequence variations in the amino- and carboxy-terminal parts of the surface envelope glycoprotein of HTLV type 1 induce specific neutralizing antibodies.

    abstract::The surface envelope glycoprotein gp46 of the human T cell leukemia virus type 1 elicits a strong immune response. Its protective role against HTLV-1 infection in animal models is well established, suggesting that recombinant envelope glycoproteins or synthetic peptides could be used as an effective vaccine. However, ...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/08892220150503708

    authors: Tallet B,Astier-Gin T,Moynet D,Londos-Gagliardi D,Guillemain B

    更新日期:2001-03-01 00:00:00

  • Simian Immunodeficiency Virus Infection Increases Blood Ethanol Concentration Duration After Both Acute and Chronic Administration.

    abstract::Alcohol use disorder (AUD) is a frequent comorbidity among people living with HIV/AIDS (PLWHA). Alcohol consumption is a significant predictor of nonadherence to antiretroviral therapy (ART), as well as worsening immunological and virological indicators among PLWHA. Clinical studies indicate that higher viral loads in...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/AID.2017.0195

    authors: Simon L,Siggins R,Winsauer P,Brashear M,Ferguson T,Mercante D,Song K,Vande Stouwe C,Nelson S,Bagby G,Amedee A,Molina PE

    更新日期:2018-02-01 00:00:00

  • Seroepidemiological and molecular studies of human T cell lymphotropic virus type II, subtype b, in isolated groups of Mataco and Toba Indians of northern Argentina.

    abstract::We studied plasma samples from 2082 Mataco Indians living in 22 different communities in the western part of Formosa Province, northern Argentina. Samples were screened for HTLV-I/II antibodies by particle agglutination assay. All positive or borderline samples were then tested by an immunofluorescence assay (IFA) on ...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/088922299311150

    authors: Biglione M,Vidan O,Mahieux R,de Colombo M,de los Angeles de Basualdo M,Bonnet M,Pankow G,De Efron MA,Zorrilla A,Tekaia F,Murphy E,de Thé G,Gessain A

    更新日期:1999-03-20 00:00:00

  • Designing preclinical perceptibility measures to evaluate topical vaginal gel formulations: relating user sensory perceptions and experiences to formulation properties.

    abstract::Abstract The effectiveness of any biomedical prevention technology relies on both biological efficacy and behavioral adherence. Microbicide trials have been hampered by low adherence, limiting the ability to draw meaningful conclusions about product effectiveness. Central to this problem may be an inadequate conceptua...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/AID.2013.0099

    authors: Morrow KM,Fava JL,Rosen RK,Vargas S,Shaw JG,Kojic EM,Kiser PF,Friend DR,Katz DF,Project Link Study Team.

    更新日期:2014-01-01 00:00:00

  • Maintaining low HIV type 1 env genetic diversity among injection drug users infected with a B/C recombinant and CRF01_AE HIV type 1 in southern China.

    abstract::HIV-1 outbreaks in Guangxi Province, southern China were initiated from two separate border cities in 1996 and 1997. Drug users in Pingxiang City, which borders Vietnam, were infected with CRF01_AE HIV-1, and drug users in Baise City, which borders Yunan Province, were infected with a novel B/C recombinant HIV-1. Sinc...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/08892220252779719

    authors: Yu XF,Liu W,Chen J,Kong W,Liu B,Zhu Q,Liang F,McCutchan F,Piyasirisilp S,Lai S

    更新日期:2002-01-20 00:00:00

  • Spreading of HIV-1 subtype G and envB/gagG recombinant strains among injecting drug users in Lisbon, Portugal.

    abstract::We have evaluated the genetic diversity of HIV-1 strains infecting injecting drug users (IDUs) in Lisbon, Portugal. Heteroduplex mobility assay and/or phylogenetic analysis revealed that env (C2V3C3 or gp41) subtype B is present in 63.7% of the 135 viral samples studied, followed by subtypes G (23.7%), A (6.7%), F (5....

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/088922203766774568

    authors: Esteves A,Parreira R,Piedade J,Venenno T,Franco M,Germano de Sousa J,Patrício L,Brum P,Costa A,Canas-Ferreira WF

    更新日期:2003-06-01 00:00:00

  • Serum concentrations of fibroblast growth factor 2 are increased in HIV type 1-infected patients and inversely related to survival probability.

    abstract::HIV-1-infected patients develop a generalized vasculopathy that is clinically most evident as Kaposi's sarcoma (KS), a multifocally appearing endothelial cell-derived tumor. Fibroblast growth factor 2 (FGF-2) is a potent autocrine and paracrine mitogen of endothelial cells and has been implicated in the cell prolifera...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/088922201300343717

    authors: Ascherl G,Sgadari C,Bugarini R,Bogner J,Schatz O,Ensoli B,Stürzl M

    更新日期:2001-07-20 00:00:00

  • Predominance of three NF-kappaB binding sites in the long terminal repeat region of HIV Type 1 subtype C isolates from Zambia.

    abstract::Human immunodeficiency virus type-1 (HIV-1) is a leading cause of mortality and morbidity in the world, with almost 46 million people infected globally. HIV-1 subtype C accounts for 55% of these infections. In Zambia, the majority of HIV-1 infections are subtype C. However, to its north most countries have non-subtype...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2005.21.901

    authors: Munkanta M,Handema R,Kasai H,Gondwe C,Deng X,Yamashita A,Asagi T,Yamamoto N,Ito M,Kasolo F,Terunuma H

    更新日期:2005-10-01 00:00:00

  • CCR5 is the major coreceptor used by HIV-1 subtype C isolates from patients with active tuberculosis.

    abstract::Tuberculosis (TB) is the major opportunistic infection of HIV-infected patients in developing countries and is associated with activation of the immune system and increased HIV-1 expression. The aim of this study was to explore the biological properties of HIV-1 isolates from patients with active TB. Ten HIV-1 subtype...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/088922201750236979

    authors: Morris L,Cilliers T,Bredell H,Phoswa M,Martin DJ

    更新日期:2001-05-20 00:00:00

  • Lethal mutagenesis of HIV by mutagenic ribonucleoside analogs.

    abstract::The extraordinarily high mutation rate of HIV suggests that the viral population exists near the threshold for viral viability. An increase in mutation could mediate a lethal increase in the already high proportion of defective viruses. We initially tested this hypothesis by culturing HIV-infected cells in mutagenic d...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/088922200309539

    authors: Loeb LA,Mullins JI

    更新日期:2000-01-01 00:00:00

  • Conformation-Dependent Interactions Between HIV-1 Envelope Glycoproteins and Broadly Neutralizing Antibodies.

    abstract::HIV type 1 (HIV-1) envelope glycoproteins (Env) mediate virus entry and are the target of neutralizing antibodies. Binding of the metastable HIV-1 Env trimer to the CD4 receptor triggers structural rearrangements that mediate Env conformational transitions from a closed conformation to a more open state through an int...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章,评审

    doi:10.1089/AID.2018.0102

    authors: Flemming J,Wiesen L,Herschhorn A

    更新日期:2018-09-01 00:00:00

  • HIV type 1-mediated downregulation of HLA-B*57/B*5801 proteins on elite suppressor CD4+ T cells.

    abstract::Elite controllers or suppressors (ES) are HIV-1-infected patients who maintain viral loads of <50 copies/ml without antiretroviral therapy. While HLA-B*57 and B*5801 alleles are overrepresented in ES, many HLA-B*57/B*5801 patients become chronic progressors (CP). We show here that HIV-1 infection results in similar le...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2010.0144

    authors: Sampah ME,Ceccato CM,Blankson JN

    更新日期:2011-02-01 00:00:00

  • Neutralizing antibodies and the course of HIV-induced disease.

    abstract::The capacity to neutralize the human immunodeficiency virus (HIV) in vitro was examined in 52 sera obtained from 23 seropositive individuals in addition to 7 negative control sera. Neutralization was measured as the activity of a serum to protect MT-4 cells against the cytopathic effect of HTLV-IIIB. Virus neutralizat...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1987.3.157

    authors: Wendler I,Bienzle U,Hunsmann G

    更新日期:1987-07-01 00:00:00

  • Efficacy and safety of three doses of tipranavir boosted with ritonavir in treatment-experienced HIV type-1 infected patients.

    abstract::The efficacy, safety, and pharmacokinetics of three doses of tipranavir/ritonavir (TPV/r) in highly treatment-experienced human immunodeficiency virus (HIV)-1-infected patients with protease inhibitor (PI)-resistant isolates were evaluated. A 24-week multicenter, double-blind, randomized, dose-finding trial was conduc...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1089/aid.2006.0178

    authors: Gathe JC Jr,Pierone G,Piliero P,Arasteh K,Rubio R,Lalonde RG,Cooper D,Lazzarin A,Kohlbrenner VM,Dohnanyi C,Sabo J,Mayers D

    更新日期:2007-02-01 00:00:00

  • Short communication: the number of HIV major NRTI mutations correlates directly with other antiretroviral-associated mutations and indirectly with replicative capacity and reduced drug susceptibility.

    abstract::While it is known that selection for specific HIV-1 drug resistance-associated mutations (DRM) occurs following ART failure, the patterns of resistance mutations, reduced susceptibility (RS), and replicative capacity (RC) that appear as the number of major NRTI mutations increases have been less well-studied. These ch...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2007.0188

    authors: Ross L,Parkin N,Lanier R

    更新日期:2008-04-01 00:00:00

  • Rate and predictors of non-AIDS events in a cohort of HIV-infected patients with a CD4 T cell count above 500 cells/mm³.

    abstract::The reduction of risk of non-AIDS events after combined antiretroviral therapy (cART) initiation and the crude incidence rate (CIR) of these events in patients who control the viral load without cART (controllers) in a cohort of 574 antiretroviral-naive patients with a baseline CD4 T cell count above 500 cells/mm³ wer...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/AID.2012.0367

    authors: Lucero C,Torres B,León A,Calvo M,Leal L,Pérez I,Plana M,Arnedo M,Mallolas J,Gatell JM,García F

    更新日期:2013-08-01 00:00:00

  • Cellular proviral HIV type 1 DNA load persists after long-term RT-inhibitor therapy in HIV type 1 infected persons.

    abstract::In a set of 42 antiretroviral naive HIV-1 infected persons who were treated with either Zidovudine (AZT) monotherapy, or a combination of AZT + ddC (Zalcitabine) or AZT + ddI (Didanosine), the HIV-1 DNA load was measured by competitive polymerase chain reaction (PCR) and related to the HIV-1 RNA load in plasma, the CD...

    journal_title:AIDS research and human retroviruses

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1089/aid.1998.14.1053

    authors: Bruisten SM,Reiss P,Loeliger AE,van Swieten P,Schuurman R,Boucher CA,Weverling GJ,Huisman JG

    更新日期:1998-08-10 00:00:00

  • Identification of the DC-SIGN-interactive domains on the envelope glycoprotein of HIV-1 CRF07_BC.

    abstract::DC-SIGN, a C-type lection expressed on dendritic cells, enhances HIV-1 infection in cis and in trans. HIV-1 circulating recombinant form (CRF) 07_BC viruses have been the predominant strain found among injection drug users in southern China and Taiwan. The goal of this study was to map the DC-SIGN-interactive domain o...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/AID.2010.0215

    authors: Liao CF,Wang SF,Lin YT,Ho DD,Chen YM

    更新日期:2011-08-01 00:00:00

  • Rapid alternation of drug therapy is highly efficient in suppressing the emergence of mutant drug-resistant HIV strains in cell culture.

    abstract::We evaluated the effect of drug alternation on human immunodeficiency virus type 1 (HIV-1) suppression and emergence of resistant virus strains in CEM cell cultures. Rapid, that is, twice weekly, alternation of lamivudine and nevirapine (at 0.1 microg/ml) at the time of each subcultivation resulted in a long-term supp...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/088922201753342031

    authors: Balzarini J,De Clercq E

    更新日期:2001-11-20 00:00:00

  • Detection of HIV-1 genome in leukocytes of human colostrum from anti-HIV-1 seropositive mothers.

    abstract::In order to obtain more information about the presence of HIV-1 in mononuclear cells of colostrum, research was carried out on both the HIV-1 genome in the cellular fraction of colostrum and the viral antibody in cell-free colostrum of eight anti-HIV-1 seropositive asymptomatic mothers. In five cases cell fractions of...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1992.8.1283

    authors: Vonesch N,Sturchio E,Humani AC,Cordiali Fei P,Cosenza D,Caprilli F,Pezzella M

    更新日期:1992-07-01 00:00:00

  • Increasing CTL targeting of conserved sequences during early HIV-1 infection is correlated to decreasing viremia.

    abstract::Early HIV-1 infection is marked by rapid evolution of both CD8(+) T lymphocyte (CTL) epitope targeting and viral sequences, while chronic infection demonstrates relative stability of these parameters. To examine the interactions of changing CTL targeting and viremia in early infection, we assessed CTL targeting and vi...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2010.0183

    authors: Yang OO,Daar ES,Ng HL,Shih R,Jamieson BD

    更新日期:2011-04-01 00:00:00

  • Near full-length sequence analysis of a Unique CRF01_AE/B recombinant from Kuala Lumpur, Malaysia.

    abstract::A new HIV-1 circulating recombinant form (CRF), CRF33_01B, has been identified in Malaysia. Concurrently we found a unique recombinant form (URF), that is, the HIV-1 isolate 06MYKLD46, in Kuala Lumpur, Malaysia. It is composed of B or a Thai variant of the B subtype (B') and CRF01_AE. Here, we determined the near full...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2007.0056

    authors: Lau KA,Wang B,Kamarulzaman A,Ng KP,Saksena NK

    更新日期:2007-09-01 00:00:00