当前位置： SCI文献检索 > Retrovirology期刊下所有文献 > Akt inhibitors as an HIV-1 infected macrophage-specific anti-viral therapy.

Akt inhibitors as an HIV-1 infected macrophage-specific anti-viral therapy.

Abstract：

BACKGROUND:Unlike CD4+ T cells, HIV-1 infected macrophages exhibit extended life span even upon stress, consistent with their in vivo role as long-lived HIV-1 reservoirs. RESULTS:Here, we demonstrate that PI3K/Akt inhibitors, including clinically available Miltefosine, dramatically reduced HIV-1 production from long-living virus-infected macrophages. These PI3K/Akt inhibitors hyper-sensitize infected macrophages to extracellular stresses that they are normally exposed to, and eventually lead to cell death of infected macrophages without harming uninfected cells. Based on the data from these Akt inhibitors, we were able to further investigate how HIV-1 infection utilizes the PI3K/Akt pathway to establish the cytoprotective effect of HIV-1 infection, which extends the lifespan of infected macrophages, a key viral reservoir. First, we found that HIV-1 infection activates the well characterized pro-survival PI3K/Akt pathway in primary human macrophages, as reflected by decreased PTEN protein expression and increased Akt kinase activity. Interestingly, the expression of HIV-1 or SIV Tat is sufficient to mediate this cytoprotective effect, which is dependent on the basic domain of Tat - a region that has previously been shown to bind p53. Next, we observed that this interaction appears to contribute to the downregulation of PTEN expression, since HIV-1 Tat was found to compete with PTEN for p53 binding; this is known to result in p53 destabilization, with a consequent reduction in PTEN protein production. CONCLUSION:Since HIV-1 infected macrophages display highly elevated Akt activity, our results collectively show that PI3K/Akt inhibitors may be a novel therapy for interfering with the establishment of long-living HIV-1 infected reservoirs.

journal_name

Retrovirology

journal_title

Retrovirology

authors

Chugh P,Bradel-Tretheway B,Monteiro-Filho CM,Planelles V,Maggirwar SB,Dewhurst S,Kim B

doi

10.1186/1742-4690-5-11

subject

Has Abstract

pub_date

2008-01-31 00:00:00

pages

11

issn

1742-4690

pii

1742-4690-5-11

journal_volume

5

pub_type

杂志文章

相关文献

Retrovirology文献大全
  • Modulation of HIV-1 Gag NC/p1 cleavage efficiency affects protease inhibitor resistance and viral replicative capacity.

    abstract：BACKGROUND:Mutations in the substrate of HIV-1 protease, especially changes in the NC/p1 cleavage site, can directly contribute to protease inhibitor (PI) resistance and also compensate for defects in viral replicative capacity (RC) due to a drug resistant protease. These NC/p1 changes are known to enhance processing o...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/1742-4690-9-29

    authors： van Maarseveen NM,Andersson D,Lepšík M,Fun A,Schipper PJ,de Jong D,Boucher CA,Nijhuis M

    更新日期：2012-04-01 00:00:00

  • HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms.

    abstract：:The glycan supersite centered on N332 in the V3 base of the HIV-1 envelope (Env) is a target for broadly neutralizing antibodies (bnAbs) such as PGT121 and PGT128. In this study, we examined the basis of resistance of HIV-1 clade C Envs obtained from broadly cross neutralizing (BCN) plasma of an Indian donor with N332...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/s12977-016-0297-2

    authors： Deshpande S,Patil S,Kumar R,Hermanus T,Murugavel KG,Srikrishnan AK,Solomon S,Morris L,Bhattacharya J

    更新日期：2016-08-30 00:00:00

  • Preferences for the selection of unique tRNA primers revealed from analysis of HIV-1 replication in peripheral blood mononuclear cells.

    abstract：BACKGROUND:All human immunodeficiency virus (HIV-1) uses a host tRNALys,3 as the primer for reverse transcription. The tRNALys,3 is bound to a region on the HIV-1 genome, the primer-binding site (PBS), that is complementary to the 18 terminal nucleotides of tRNALys,3. How HIV-1 selects the tRNA from the intracellular m...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/1742-4690-2-21

    authors： Moore-Rigdon KL,Kosloff BR,Kirkman RL,Morrow CD

    更新日期：2005-03-24 00:00:00

  • HIV-1 envelope replication and α4β7 utilization among newly infected subjects and their corresponding heterosexual partners.

    abstract：BACKGROUND:Previous studies suggest that active selection limits the number of HIV-1 variants acquired by a newly infected individual from the diverse variants circulating in the transmitting partner. We compared HIV-1 envelopes from 9 newly infected subjects and their linked transmitting partner to explore potential m...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/1742-4690-10-162

    authors： Pena-Cruz V,Etemad B,Chatziandreou N,Nyein PH,Stock S,Reynolds SJ,Laeyendecker O,Gray RH,Serwadda D,Lee SJ,Quinn TC,Sagar M

    更新日期：2013-12-26 00:00:00

  • The XVI International Conference on AIDS: the place to be!

    abstract：:This editorial represents a plea to retrovirologists to attend the XVI International Conference on AIDS that will take place in Toronto, Canada between August 13-18, 2006. In short, it is vital that politicians and opinion leaders understand that basic scientists are no less committed to the worldwide battle against H...

    journal_title：Retrovirology

    pub_type： 社论

    doi：10.1186/1742-4690-3-9

    authors： Wainberg MA

    更新日期：2006-02-03 00:00:00

  • Tenofovir treatment augments anti-viral immunity against drug-resistant SIV challenge in chronically infected rhesus macaques.

    abstract：BACKGROUND:Emergence of drug-resistant strains of human immunodeficiency virus type 1 (HIV-1) is a major obstacle to successful antiretroviral therapy (ART) in HIV-infected patients. Whether antiviral immunity can augment ART by suppressing replication of drug-resistant HIV-1 in humans is not well understood, but can b...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/1742-4690-3-97

    authors： Metzner KJ,Binley JM,Gettie A,Marx P,Nixon DF,Connor RI

    更新日期：2006-12-21 00:00:00

  • Functional analysis of human T lymphotropic virus type 2 Tax proteins.

    abstract：BACKGROUND:The Tax proteins encoded by human T lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) are transcriptional activators of both the viral long terminal repeat (LTR) and cellular promoters via the CREB and NFkB pathways. In contrast to HTLV-1, HTLV-2 has been classified into four distinct genetic subtypes A...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/1742-4690-3-20

    authors： Sheehy N,Lillis L,Watters K,Lewis M,Gautier V,Hall W

    更新日期：2006-03-21 00:00:00

  • Molecular mechanisms by which HERV-K Gag interferes with HIV-1 Gag assembly and particle infectivity.

    abstract：BACKGROUND:Human endogenous retroviruses (HERVs), the remnants of ancient retroviral infections, constitute approximately 8% of human genomic DNA. Since HERV-K Gag expression is induced by HIV-1 Tat in T cells, induced HERV-K proteins could affect HIV-1 replication. Indeed, previously we showed that HERV-K Gag and HIV-...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/s12977-017-0351-8

    authors： Monde K,Terasawa H,Nakano Y,Soheilian F,Nagashima K,Maeda Y,Ono A

    更新日期：2017-04-26 00:00:00

  • No evidence of XMRV in prostate cancer cohorts in the Midwestern United States.

    abstract：BACKGROUND:Xenotropic murine leukemia virus (MLV)-related virus (XMRV) was initially identified in prostate cancer (PCa) tissue, particularly in the prostatic stromal fibroblasts, of patients homozygous for the RNASEL R462Q mutation. A subsequent study reported XMRV antigens in malignant prostatic epithelium and associ...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/1742-4690-8-23

    authors： Sakuma T,Hué S,Squillace KA,Tonne JM,Blackburn PR,Ohmine S,Thatava T,Towers GJ,Ikeda Y

    更新日期：2011-03-29 00:00:00

  • Low-level alternative tRNA priming of reverse transcription of HIV-1 and SIV in vivo.

    abstract：BACKGROUND:Reverse transcription (RT) of HIV and SIV is initiated by the binding of the acceptor stem of tRNALys3 to the primer binding site (PBS) of the viral RNA genome. Previous studies have suggested that this tRNALys3 is not the only molecule capable of priming reverse transcription, and that at least one other ly...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/s12977-019-0473-2

    authors： Fennessey CM,Camus C,Immonen TT,Reid C,Maldarelli F,Lifson JD,Keele BF

    更新日期：2019-04-04 00:00:00

  • The co-receptor signaling model of HIV-1 pathogenesis in peripheral CD4 T cells.

    abstract：:HIV-mediated CD4 depletion is the hallmark of AIDS and is the most reliable predictor of disease progression. While HIV replication is associated with CD4 depletion in general, plasma viremia by itself predicts the rate of CD4 loss only minimally in untreated patients. To resolve this paradox, I hypothesize the existe...

    journal_title：Retrovirology

    pub_type： 社论

    doi：10.1186/1742-4690-6-41

    authors： Wu Y

    更新日期：2009-05-01 00:00:00

  • HIV integration and the establishment of latency in CCL19-treated resting CD4(+) T cells require activation of NF-κB.

    abstract：BACKGROUND:Eradication of HIV cannot be achieved with combination antiretroviral therapy (cART) because of the persistence of long-lived latently infected resting memory CD4(+) T cells. We previously reported that HIV latency could be established in resting CD4(+) T cells in the presence of the chemokine CCL19. To defi...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/s12977-016-0284-7

    authors： Saleh S,Lu HK,Evans V,Harisson D,Zhou J,Jaworowski A,Sallmann G,Cheong KY,Mota TM,Tennakoon S,Angelovich TA,Anderson J,Harman A,Cunningham A,Gray L,Churchill M,Mak J,Drummer H,Vatakis DN,Lewin SR,Cameron PU

    更新日期：2016-07-26 00:00:00

  • Primate lentiviral Nef proteins deregulate T-cell development by multiple mechanisms.

    abstract：BACKGROUND:A nef gene is present in all primate lentiviral genomes and is important for high viral loads and progression to AIDS in human or experimental macaque hosts of HIV or SIV, respectively. In these hosts, infection of the thymus results in a decreased output of naive T cells that may contribute to the developme...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/1742-4690-10-137

    authors： Van Nuffel A,Ariën KK,Stove V,Schindler M,O'Neill E,Schmökel J,Van de Walle I,Naessens E,Vanderstraeten H,Van Landeghem K,Taghon T,Pulkkinen K,Saksela K,Garcia JV,Fackler OT,Kirchhoff F,Verhasselt B

    更新日期：2013-11-15 00:00:00

  • Discovery of a diaminoquinoxaline benzenesulfonamide antagonist of HIV-1 Nef function using a yeast-based phenotypic screen.

    abstract：BACKGROUND:HIV-1 Nef is a viral accessory protein critical for AIDS progression. Nef lacks intrinsic catalytic activity and binds multiple host cell signaling proteins, including Hck and other Src-family tyrosine kinases. Nef binding induces constitutive Hck activation that may contribute to HIV pathogenesis by promoti...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/1742-4690-10-135

    authors： Trible RP,Narute P,Emert-Sedlak LA,Alvarado JJ,Atkins K,Thomas L,Kodama T,Yanamala N,Korotchenko V,Day BW,Thomas G,Smithgall TE

    更新日期：2013-11-14 00:00:00

  • The pathogenesis of HIV infection: stupid may not be so dumb after all.

    abstract：:In the mid-1990's, researchers hypothesized, based on new viral load data, that HIV-1 causes CD4+ T-cell depletion by direct cytopathic effect. New data from non-human primate studies has raised doubts about this model of HIV-1 pathogenesis. Despite having high levels of viremia, most SIV infections are well tolerated...

    journal_title：Retrovirology

    pub_type： 社论

    doi：10.1186/1742-4690-3-60

    authors： Smith SM

    更新日期：2006-09-08 00:00:00

  • Distinct gene expression signatures induced by viral transactivators of different HTLV-1 subgroups that confer a different risk of HAM/TSP.

    abstract：BACKGROUND:Among human T cell leukemia virus type 1 (HTLV-1)-infected individuals, there is an association between HTLV-1 tax subgroups (subgroup-A or subgroup-B) and the risk of HAM/TSP in the Japanese population. To investigate the role of HTLV-1 subgroups in viral pathogenesis, we studied the functional difference i...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/s12977-018-0454-x

    authors： Naito T,Yasunaga JI,Mitobe Y,Shirai K,Sejima H,Ushirogawa H,Tanaka Y,Nakamura T,Hanada K,Fujii M,Matsuoka M,Saito M

    更新日期：2018-11-06 00:00:00

  • Identification of small molecule modulators of HIV-1 Tat and Rev protein accumulation.

    abstract：BACKGROUND:HIV-1 replication is critically dependent upon controlled processing of its RNA and the activities provided by its encoded regulatory factors Tat and Rev. A screen of small molecule modulators of RNA processing identified several which inhibited virus gene expression, affecting both relative abundance of spe...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/s12977-017-0330-0

    authors： Balachandran A,Wong R,Stoilov P,Pan S,Blencowe B,Cheung P,Harrigan PR,Cochrane A

    更新日期：2017-01-26 00:00:00

  • Automethylation of protein arginine methyltransferase 6 (PRMT6) regulates its stability and its anti-HIV-1 activity.

    abstract：BACKGROUND:Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that methylates arginine residues on histones and transcription factors. In addition, PRMT6 inhibits HIV-1 replication in cell culture by directly methylating and interfering with the functions of several HIV-1 proteins, i.e. Tat, Rev and nucle...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/1742-4690-10-73

    authors： Singhroy DN,Mesplède T,Sabbah A,Quashie PK,Falgueyret JP,Wainberg MA

    更新日期：2013-07-17 00:00:00

  • Stabilization of the β-hairpin in Mason-Pfizer monkey virus capsid protein- a critical step for infectivity.

    abstract：BACKGROUND:Formation of a mature core is a crucial event for infectivity of retroviruses such as Mason-Pfizer monkey virus (M-PMV). The process is triggered by proteolytic cleavage of the polyprotein precursor Gag, which releases matrix, capsid (CA), and nucleocapsid proteins. Once released, CA assembles to form a matu...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/s12977-014-0094-8

    authors： Obr M,Hadravová R,DoleŽal M,KříŽová I,Papoušková V,Zídek L,Hrabal R,Ruml T,Rumlová M

    更新日期：2014-10-30 00:00:00

  • Increased susceptibility of CD4+ T cells from elderly individuals to HIV-1 infection and apoptosis is associated with reduced CD4 and enhanced CXCR4 and FAS surface expression levels.

    abstract：BACKGROUND:Elderly HIV-1 infected individuals progress to AIDS more frequently and rapidly than people becoming infected at a young age. To identify possible reasons for these differences in clinical progression, we performed comprehensive phenotypic analyses of CD4+ T cells from uninfected young and elderly individual...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/s12977-015-0213-1

    authors： Heigele A,Joas S,Regensburger K,Kirchhoff F

    更新日期：2015-10-09 00:00:00

  • Targeted infection of HIV-1 Env expressing cells by HIV(CD4/CXCR4) vectors reveals a potential new rationale for HIV-1 mediated down-modulation of CD4.

    abstract：BACKGROUND:Efficient targeted gene transfer and cell type specific transgene expression are important for the safe and effective expression of transgenes in vivo. Enveloped viral vectors allow insertion of exogenous membrane proteins into their envelopes, which could potentially aid in the targeted transduction of spec...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/1742-4690-2-80

    authors： Ye Z,Harmison GG,Ragheb JA,Schubert M

    更新日期：2005-12-21 00:00:00

  • Reactivation from latency displays HIV particle budding at plasma membrane, accompanying CD44 upregulation and recruitment.

    abstract：BACKGROUND:It has been accepted that HIV buds from the cell surface in T lymphocytes, whereas in macrophages it buds into intracellular endosomes. Recent studies, on the other hand, suggest that HIV preferentially buds from the cell surface even in monocytic cells. However, most studies are based on observations in acu...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/1742-4690-6-63

    authors： Suyama M,Daikoku E,Goto T,Sano K,Morikawa Y

    更新日期：2009-07-13 00:00:00

  • STLV-1 as a model for studying HTLV-1 infection.

    abstract：:Few years after HTLV-1 identification and isolation in humans, STLV-1, its simian counterpart, was discovered. It then became clear that STLV-1 is present almost in all simian species. Subsequent molecular epidemiology studies demonstrated that, apart from HTLV-1 subtype A, all human subtypes have a simian homolog. As...

    journal_title：Retrovirology

    pub_type： 杂志文章,评审

    doi：10.1186/s12977-019-0503-0

    authors： Jégado B,Kashanchi F,Dutartre H,Mahieux R

    更新日期：2019-12-16 00:00:00

  • Acquisition of CD4-dependence by CD4-independent SIV passaged in human peripheral blood mononuclear cells.

    abstract：BACKGROUND:Chemokine receptors (CKRs), the primordial receptors for primate lentiviruses, are sufficient to mediate virus-cell fusion. Several different fusogenic CKRs and related receptors provide a broad potential host cell range, presumably advantageous for viral spread within a given infected individual, and across...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/1742-4690-9-61

    authors： Iyengar S,Schwartz DH

    更新日期：2012-07-25 00:00:00

  • Generation and validation of a highly sensitive bioluminescent HIV-1 reporter vector that simplifies measurement of virus release.

    abstract：BACKGROUND:The continued persistence of HIV-1 as a public health concern due to the lack of a cure calls for the development of new tools for studying replication of the virus. Here, we used NanoLuc, a small and extremely bright luciferase protein, to develop an HIV-1 bioluminescent reporter virus that simplifies funct...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/s12977-020-00521-5

    authors： Kirui J,Freed EO

    更新日期：2020-05-19 00:00:00

  • Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase.

    abstract：BACKGROUND:The 18 residue tail abutting the SH3 fold that comprises the heart of the C-terminal domain is the only part of HIV-1 integrase yet to be visualized by structural biology. To ascertain the role of the tail region in integrase function and HIV-1 replication, a set of deletion mutants that successively lacked ...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/1742-4690-6-94

    authors： Dar MJ,Monel B,Krishnan L,Shun MC,Di Nunzio F,Helland DE,Engelman A

    更新日期：2009-10-19 00:00:00

  • The S40 residue in HIV-1 Gag p6 impacts local and distal budding determinants, revealing additional late domain activities.

    abstract：BACKGROUND:HIV-1 budding is directed primarily by two motifs in Gag p6 designated as late domain-1 and -2 that recruit ESCRT machinery by binding Tsg101 and Alix, respectively, and by poorly characterized determinants in the capsid (CA) domain. Here, we report that a conserved Gag p6 residue, S40, impacts budding media...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/1742-4690-10-143

    authors： Watanabe SM,Chen MH,Khan M,Ehrlich L,Kemal KS,Weiser B,Shi B,Chen C,Powell M,Anastos K,Burger H,Carter CA

    更新日期：2013-11-21 00:00:00

  • Identification of the feline foamy virus Bet domain essential for APOBEC3 counteraction.

    abstract：BACKGROUND:APOBEC3 (A3) proteins restrict viral replication by cytidine deamination of viral DNA genomes and impairing reverse transcription and integration. To escape this restriction, lentiviruses have evolved the viral infectivity factor (Vif), which binds A3 proteins and targets them for proteolytic degradation. In...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/1742-4690-10-76

    authors： Lukic DS,Hotz-Wagenblatt A,Lei J,Räthe AM,Mühle M,Denner J,Münk C,Löchelt M

    更新日期：2013-07-24 00:00:00

  • 'Libyan Trial': a verdict running counter to scientific evidence.

    abstract：:Sidaction's appeal regarding the sentencing of medical personnels in the Libyan-HIV infection cases. ...

    journal_title：Retrovirology

    pub_type： 社论

    doi：10.1186/1742-4690-3-98

    authors： Fleutelot E

    更新日期：2006-12-27 00:00:00

  • Evolution and gene capture in ancient endogenous retroviruses - insights from the crocodilian genomes.

    abstract：BACKGROUND:Crocodilians are thought to be hosts to a diverse and divergent complement of endogenous retroviruses (ERVs) but a comprehensive investigation is yet to be performed. The recent sequencing of three crocodilian genomes provides an opportunity for a more detailed and accurate representation of the ERV diversit...

    journal_title：Retrovirology

    pub_type： 杂志文章

    doi：10.1186/s12977-014-0071-2

    authors： Chong AY,Kojima KK,Jurka J,Ray DA,Smit AF,Isberg SR,Gongora J

    更新日期：2014-12-12 00:00:00