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
Retrovirologyjournal_title
Retrovirologyauthors
Nangola S,Urvoas A,Valerio-Lepiniec M,Khamaikawin W,Sakkhachornphop S,Hong SS,Boulanger P,Minard P,Tayapiwatana Cdoi
10.1186/1742-4690-9-17subject
Has Abstractpub_date
2012-02-20 00:00:00pages
17issn
1742-4690pii
1742-4690-9-17journal_volume
9pub_type
杂志文章相关文献
Retrovirology文献大全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
更新日期:2018-02-17 00:00:00
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
更新日期:2017-11-09 00:00:00
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
更新日期:2012-04-01 00:00:00
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
更新日期:2007-10-15 00:00:00
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
更新日期:2006-02-03 00:00:00
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
更新日期:2012-10-15 00:00:00
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
更新日期:2005-06-10 00:00:00
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
更新日期:2004-07-30 00:00:00
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
更新日期:2009-05-01 00:00:00
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
更新日期:2009-04-08 00:00:00
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
更新日期:2009-10-19 00:00:00
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
更新日期:2016-05-03 00:00:00
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
更新日期:2009-05-06 00:00:00
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
更新日期:2020-05-19 00:00:00
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
更新日期:2018-12-17 00:00:00
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
更新日期:2008-07-01 00:00:00
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
更新日期:2012-12-11 00:00:00
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
更新日期:2006-01-27 00:00:00
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
更新日期:2018-10-23 00:00:00
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
更新日期:2011-05-13 00:00:00
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
更新日期:2005-07-02 00:00:00
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
更新日期:2017-01-20 00:00:00
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
更新日期:2006-11-08 00:00:00
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
更新日期:2018-11-06 00:00:00
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
更新日期:2008-02-01 00:00:00
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
更新日期:2012-08-13 00:00:00
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
更新日期:2007-01-09 00:00:00
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
更新日期:2008-09-22 00:00:00
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
更新日期:2012-12-05 00:00:00
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
更新日期:2019-11-06 00:00:00