Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein.

Abstract:

BACKGROUND:Ankyrins are cellular mediators of a number of essential protein-protein interactions. Unlike intrabodies, ankyrins are composed of highly structured repeat modules characterized by disulfide bridge-independent folding. Artificial ankyrin molecules, designed to target viral components, might act as intracellular antiviral agents and contribute to the cellular immunity against viral pathogens such as HIV-1. RESULTS:A phage-displayed library of artificial ankyrins was constructed, and screened on a polyprotein made of the fused matrix and capsid domains (MA-CA) of the HIV-1 Gag precursor. An ankyrin with three modules named Ank(GAG)1D4 (16.5 kDa) was isolated. Ank(GAG)1D4 and MA-CA formed a protein complex with a stoichiometry of 1:1 and a dissociation constant of K(d) ~ 1 μM, and the Ank(GAG)1D4 binding site was mapped to the N-terminal domain of the CA, within residues 1-110. HIV-1 production in SupT1 cells stably expressing Ank(GAG)1D4 in both N-myristoylated and non-N-myristoylated versions was significantly reduced compared to control cells. Ank(GAG)1D4 expression also reduced the production of MLV, a phylogenetically distant retrovirus. The Ank(GAG)1D4-mediated antiviral effect on HIV-1 was found to occur at post-integration steps, but did not involve the Gag precursor processing or cellular trafficking. Our data suggested that the lower HIV-1 progeny yields resulted from the negative interference of Ank(GAG)1D4-CA with the Gag assembly and budding pathway. CONCLUSIONS:The resistance of Ank(GAG)1D4-expressing cells to HIV-1 suggested that the CA-targeted ankyrin Ank(GAG)1D4 could serve as a protein platform for the design of a novel class of intracellular inhibitors of HIV-1 assembly based on ankyrin-repeat modules.

journal_name

Retrovirology

journal_title

Retrovirology

authors

Nangola S,Urvoas A,Valerio-Lepiniec M,Khamaikawin W,Sakkhachornphop S,Hong SS,Boulanger P,Minard P,Tayapiwatana C

doi

10.1186/1742-4690-9-17

subject

Has Abstract

pub_date

2012-02-20 00:00:00

pages

17

issn

1742-4690

pii

1742-4690-9-17

journal_volume

9

pub_type

杂志文章
  • Measuring integrated HIV DNA ex vivo and in vitro provides insights about how reservoirs are formed and maintained.

    abstract::The identification of the most appropriate marker to measure reservoir size has been a great challenge for the HIV field. Quantitative viral outgrowth assay (QVOA), the reference standard to quantify the amount of replication-competent virus, has several limitations, as it is laborious, expensive, and unable to robust...

    journal_title:Retrovirology

    pub_type: 杂志文章,评审

    doi:10.1186/s12977-018-0396-3

    authors: Pinzone MR,O'Doherty U

    更新日期:2018-02-17 00:00:00

  • The HIV-1 integrase-LEDGF allosteric inhibitor MUT-A: resistance profile, impairment of virus maturation and infectivity but without influence on RNA packaging or virus immunoreactivity.

    abstract:BACKGROUND:HIV-1 Integrase (IN) interacts with the cellular co-factor LEDGF/p75 and tethers the HIV preintegration complex to the host genome enabling integration. Recently a new class of IN inhibitors was described, the IN-LEDGF allosteric inhibitors (INLAIs). Designed to interfere with the IN-LEDGF interaction during...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/s12977-017-0373-2

    authors: Amadori C,van der Velden YU,Bonnard D,Orlov I,van Bel N,Le Rouzic E,Miralles L,Brias J,Chevreuil F,Spehner D,Chasset S,Ledoussal B,Mayr L,Moreau F,García F,Gatell J,Zamborlini A,Emiliani S,Ruff M,Klaholz BP,Moog C

    更新日期:2017-11-09 00:00:00

  • 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

  • Small non-coding RNAs, mammalian cells, and viruses: regulatory interactions?

    abstract::Recent findings suggest that mammalian cells can use small non-coding RNAs (ncRNA) to regulate physiological viral infections. Here, we comment on several lines of evidence that support this concept. We discuss how viruses may in turn protect, suppress, evade, modulate, or adapt to the host cell's ncRNA regulatory sch...

    journal_title:Retrovirology

    pub_type: 社论,评审

    doi:10.1186/1742-4690-4-74

    authors: Yeung ML,Benkirane M,Jeang KT

    更新日期:2007-10-15 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

  • Caveolin-1 reduces HIV-1 infectivity by restoration of HIV Nef mediated impairment of cholesterol efflux by apoA-I.

    abstract:BACKGROUND:HIV infection results in inhibited cholesterol efflux by apolipoprotein A-I (apoA-I) in macrophages, and this impairment involves Nef mediated down-regulation and redistribution of ATP-binding cassette transporter A1 (ABCA-1). We investigated the effect of caveolin-1 (Cav-1) on the cholesterol efflux by apoA...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/1742-4690-9-85

    authors: Lin S,Nadeau PE,Wang X,Mergia A

    更新日期:2012-10-15 00:00:00

  • HIV-1 Rev oligomerization is not obligatory in the presence of an extra basic domain.

    abstract:BACKGROUND:The HIV-1 Rev regulatory protein binds as an oligomeric complex to viral RNA mediating nuclear export of incompletely spliced and non-spliced viral mRNAs encoding the viral structural proteins. However, the biological significance of the obligatory complex formation of Rev upon the viral RNA is unclear. RES...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/1742-4690-2-39

    authors: Furnes C,Arnesen T,Askjaer P,Kjems J,Szilvay AM

    更新日期:2005-06-10 00:00:00

  • The expanding role of Tax in transcription.

    abstract::The viral transactivator of HTLV-I, Tax, has long been shown to target the earliest steps of transcription by forming quaternary complexes with sequence specific transcription factors and histone-modifying enzymes in the LTR of HTLV-I. However, a new study suggests that Tax preferentially transactivates the 21-bp repe...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/1742-4690-1-19

    authors: de la Fuente C,Kashanchi F

    更新日期:2004-07-30 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

  • Induction of p21(CIP1/WAF1) expression by human T-lymphotropic virus type 1 Tax requires transcriptional activation and mRNA stabilization.

    abstract::HTLV-1 Tax can induce senescence by up-regulating the levels of cyclin-dependent kinase inhibitors p21(CIP1/WAF1) and p27(KIP1). Tax increases p27(KIP1) protein stability by activating the anaphase promoting complex/cyclosome (APC/C) precociously, causing degradation of Skp2 and inactivation of SCF(Skp2), the E3 ligas...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/1742-4690-6-35

    authors: Zhang L,Zhi H,Liu M,Kuo YL,Giam CZ

    更新日期:2009-04-08 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

  • Utilization of HIV-1 envelope V3 to identify X4- and R5-specific Tat and LTR sequence signatures.

    abstract:BACKGROUND:HIV-1 entry is a receptor-mediated process directed by the interaction of the viral envelope with the host cell CD4 molecule and one of two co-receptors, CCR5 or CXCR4. The amino acid sequence of the third variable (V3) loop of the HIV-1 envelope is highly predictive of co-receptor utilization preference dur...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/s12977-016-0266-9

    authors: Antell GC,Dampier W,Aiamkitsumrit B,Nonnemacher MR,Jacobson JM,Pirrone V,Zhong W,Kercher K,Passic S,Williams JW,Schwartz G,Hershberg U,Krebs FC,Wigdahl B

    更新日期:2016-05-03 00:00:00

  • TLR2 and TLR4 triggering exerts contrasting effects with regard to HIV-1 infection of human dendritic cells and subsequent virus transfer to CD4+ T cells.

    abstract:BACKGROUND:Recognition of microbial products through Toll-like receptors (TLRs) initiates inflammatory responses orchestrated by innate immune cells such as dendritic cells (DCs). As these cells are patrolling mucosal surfaces, a portal of entry for various pathogens including human immunodeficiency virus type-1 (HIV-1...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/1742-4690-6-42

    authors: Thibault S,Fromentin R,Tardif MR,Tremblay MJ

    更新日期:2009-05-06 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

  • Natural APOBEC3C variants can elicit differential HIV-1 restriction activity.

    abstract:BACKGROUND:The APOBEC3 (A3) family of DNA cytosine deaminases provides an innate barrier to infection by retroviruses including HIV-1. A total of five enzymes, A3C, A3D, A3F, A3G and A3H, are degraded by the viral accessory protein Vif and expressed at high levels in CD4+ T cells, the primary reservoir for HIV-1 replic...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/s12977-018-0459-5

    authors: Anderson BD,Ikeda T,Moghadasi SA,Martin AS,Brown WL,Harris RS

    更新日期:2018-12-17 00:00:00

  • Trypanosoma cruzi (Chagas' disease agent) reduces HIV-1 replication in human placenta.

    abstract:BACKGROUND:Several factors determine the risk of HIV mother-to-child transmission (MTCT), such as coinfections in placentas from HIV-1 positive mothers with other pathogens. Chagas' disease is one of the most endemic zoonoses in Latin America, caused by the protozoan Trypanosoma cruzi. The purpose of the study was to d...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/1742-4690-5-53

    authors: Dolcini GL,Solana ME,Andreani G,Celentano AM,Parodi LM,Donato AM,Elissondo N,González Cappa SM,Giavedoni LD,Martínez Peralta L

    更新日期:2008-07-01 00:00:00

  • SAMHD1 restricts HIV-1 infection in dendritic cells (DCs) by dNTP depletion, but its expression in DCs and primary CD4+ T-lymphocytes cannot be upregulated by interferons.

    abstract:BACKGROUND:SAMHD1 is an HIV-1 restriction factor in non-dividing monocytes, dendritic cells (DCs), macrophages, and resting CD4+ T-cells. Acting as a deoxynucleoside triphosphate (dNTP) triphosphohydrolase, SAMHD1 hydrolyzes dNTPs and restricts HIV-1 infection in macrophages and resting CD4+ T-cells by decreasing the i...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/1742-4690-9-105

    authors: St Gelais C,de Silva S,Amie SM,Coleman CM,Hoy H,Hollenbaugh JA,Kim B,Wu L

    更新日期:2012-12-11 00:00:00

  • Reservoir cells no longer detectable after a heterologous SHIV challenge with the synthetic HIV-1 Tat Oyi vaccine.

    abstract:BACKGROUND:Extra-cellular roles of Tat might be the main cause of maintenance of HIV-1 infected CD4 T cells or reservoir cells. We developed a synthetic vaccine based on a Tat variant of 101 residues called Tat Oyi, which was identified in HIV infected patients in Africa who did not progress to AIDS. We compared, using...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/1742-4690-3-8

    authors: Watkins JD,Lancelot S,Campbell GR,Esquieu D,de Mareuil J,Opi S,Annappa S,Salles JP,Loret EP

    更新日期:2006-01-27 00:00:00

  • The role of integration and clonal expansion in HIV infection: live long and prosper.

    abstract::Integration of viral DNA into the host genome is a central event in the replication cycle and the pathogenesis of retroviruses, including HIV. Although most cells infected with HIV are rapidly eliminated in vivo, HIV also infects long-lived cells that persist during combination antiretroviral therapy (cART). Cells wit...

    journal_title:Retrovirology

    pub_type: 杂志文章,评审

    doi:10.1186/s12977-018-0448-8

    authors: Anderson EM,Maldarelli F

    更新日期:2018-10-23 00:00:00

  • Tat RNA silencing suppressor activity contributes to perturbation of lymphocyte miRNA by HIV-1.

    abstract:BACKGROUND:MicroRNA (miRNA)-mediated RNA silencing is integral to virtually every cellular process including cell cycle progression and response to virus infection. The interplay between RNA silencing and HIV-1 is multifaceted, and accumulating evidence posits a strike-counterstrike interface that alters the cellular e...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/1742-4690-8-36

    authors: Hayes AM,Qian S,Yu L,Boris-Lawrie K

    更新日期:2011-05-13 00:00:00

  • Inhibition of Tat activity by the HEXIM1 protein.

    abstract:BACKGROUND:The positive transcription elongation factor b (P-TEFb) composed by CDK9/CyclinT1 subunits is a dedicated co-factor of HIV transcriptional transactivator Tat protein. Transcription driven by the long terminal repeat (LTR) of HIV involves formation of a quaternary complex between P-TEFb, Tat and the TAR eleme...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/1742-4690-2-42

    authors: Fraldi A,Varrone F,Napolitano G,Michels AA,Majello B,Bensaude O,Lania L

    更新日期:2005-07-02 00:00:00

  • Evidence against a role for jaagsiekte sheep retrovirus in human lung cancer.

    abstract:BACKGROUND:Jaagsiekte sheep retrovirus (JSRV) causes a contagious lung cancer in sheep and goats that can be transmitted by aerosols produced by infected animals. Virus entry into cells is initiated by binding of the viral envelope (Env) protein to a specific cell-surface receptor, Hyal2. Unlike almost all other retrov...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/s12977-017-0329-6

    authors: Miller AD,De Las Heras M,Yu J,Zhang F,Liu SL,Vaughan AE,Vaughan TL,Rosadio R,Rocca S,Palmieri G,Goedert JJ,Fujimoto J,Wistuba II

    更新日期:2017-01-20 00:00:00

  • Human Immunodeficiency Virus-Type 1 LTR DNA contains an intrinsic gene producing antisense RNA and protein products.

    abstract:BACKGROUND:While viruses have long been shown to capitalize on their limited genomic size by utilizing both strands of DNA or complementary DNA/RNA intermediates to code for viral proteins, it has been assumed that human retroviruses have all their major proteins translated only from the plus or sense strand of RNA, de...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/1742-4690-3-80

    authors: Ludwig LB,Ambrus JL Jr,Krawczyk KA,Sharma S,Brooks S,Hsiao CB,Schwartz SA

    更新日期:2006-11-08 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

  • Socioeconomic status (SES) as a determinant of adherence to treatment in HIV infected patients: a systematic review of the literature.

    abstract:OBJECTIVES:It has been shown that socioeconomic status (SES) is associated with adherence to treatment of patients with several chronic diseases. However, there is a controversy regarding the impact of SES on adherence among patients with the human immunodeficiency virus (HIV) infection or acquired immunodeficiency syn...

    journal_title:Retrovirology

    pub_type: 社论,评审

    doi:10.1186/1742-4690-5-13

    authors: Falagas ME,Zarkadoulia EA,Pliatsika PA,Panos G

    更新日期:2008-02-01 00:00:00

  • Virus-producing cells determine the host protein profiles of HIV-1 virion cores.

    abstract:BACKGROUND:Upon HIV entry into target cells, viral cores are released and rearranged into reverse transcription complexes (RTCs), which support reverse transcription and also protect and transport viral cDNA to the site of integration. RTCs are composed of viral and cellular proteins that originate from both target and...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/1742-4690-9-65

    authors: Santos S,Obukhov Y,Nekhai S,Bukrinsky M,Iordanskiy S

    更新日期:2012-08-13 00:00:00

  • Crystal structure of an FIV/HIV chimeric protease complexed with the broad-based inhibitor, TL-3.

    abstract::We have obtained the 1.7 A crystal structure of FIV protease (PR) in which 12 critical residues around the active site have been substituted with the structurally equivalent residues of HIV PR (12X FIV PR). The chimeric PR was crystallized in complex with the broad-based inhibitor TL-3, which inhibits wild type FIV an...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/1742-4690-4-1

    authors: Heaslet H,Lin YC,Tam K,Torbett BE,Elder JH,Stout CD

    更新日期:2007-01-09 00:00:00

  • How to engage Cofilin.

    abstract::In HIV-infected people, resting CD4+ T cells are the main reservoir of latent virus and the reason for the failure of drug therapy to cure HIV infection. Still, we do not have a complete understanding of the factors regulating HIV replication in these cells. A recent paper in Cell describes a new trick that the virus ...

    journal_title:Retrovirology

    pub_type: 杂志文章,评审

    doi:10.1186/1742-4690-5-85

    authors: Bukrinsky M

    更新日期:2008-09-22 00:00:00

  • A comparison of the ability of rilpivirine (TMC278) and selected analogues to inhibit clinically relevant HIV-1 reverse transcriptase mutants.

    abstract:BACKGROUND:The recently approved anti-AIDS drug rilpivirine (TMC278, Edurant) is a nonnucleoside inhibitor (NNRTI) that binds to reverse transcriptase (RT) and allosterically blocks the chemical step of DNA synthesis. In contrast to earlier NNRTIs, rilpivirine retains potency against well-characterized, clinically rele...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/1742-4690-9-99

    authors: Johnson BC,Pauly GT,Rai G,Patel D,Bauman JD,Baker HL,Das K,Schneider JP,Maloney DJ,Arnold E,Thomas CJ,Hughes SH

    更新日期:2012-12-05 00:00:00

  • NHEJ pathway is involved in post-integrational DNA repair due to Ku70 binding to HIV-1 integrase.

    abstract:BACKGROUND:HIV-1 integration results in genomic DNA gaps that are repaired by cellular DNA repair pathways. This step of the lentiviral life cycle remains poorly understood despite its crucial importance for successful replication. We and others reported that Ku70 protein of the non-homologous end joining pathway (NHEJ...

    journal_title:Retrovirology

    pub_type: 杂志文章

    doi:10.1186/s12977-019-0492-z

    authors: Knyazhanskaya E,Anisenko A,Shadrina O,Kalinina A,Zatsepin T,Zalevsky A,Mazurov D,Gottikh M

    更新日期:2019-11-06 00:00:00