11 results on '"Stéphanie De Houwer"'
Search Results
2. Inhibitors of the integrase–transportin-SR2 interaction block HIV nuclear import
- Author
-
Jonas Demeulemeester, Jolien Blokken, Stéphanie De Houwer, Lieve Dirix, Hugo Klaassen, Arnaud Marchand, Patrick Chaltin, Frauke Christ, and Zeger Debyser
- Subjects
Drug discovery ,Integrase ,Transportin-SR2 ,HIV ,Nuclear import ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background Combination antiretroviral therapy efficiently suppresses HIV replication in infected patients, transforming HIV/AIDS into a chronic disease. Viral resistance does develop however, especially under suboptimal treatment conditions such as poor adherence. As a consequence, continued exploration of novel targets is paramount to identify novel antivirals that do not suffer from cross-resistance with existing drugs. One new promising class of targets are HIV protein–cofactor interactions. Transportin-SR2 (TRN-SR2) is a β-karyopherin that was recently identified as an HIV-1 cofactor. It has been implicated in nuclear import of the viral pre-integration complex and was confirmed as a direct binding partner of HIV-1 integrase (IN). Nevertheless, consensus on its mechanism of action is yet to be reached. Results Here we describe the development and use of an AlphaScreen-based high-throughput screening cascade for small molecule inhibitors of the HIV-1 IN–TRN-SR2 interaction. False positives and nonspecific protein–protein interaction inhibitors were eliminated through different counterscreens. We identified and confirmed 2 active compound series from an initial screen of 25,608 small molecules. These compounds significantly reduced nuclear import of fluorescently labeled HIV particles. Conclusions Alphascreen-based high-throughput screening can allow the identification of compounds representing a novel class of HIV inhibitors. These results corroborate the role of the IN–TRN-SR2 interaction in nuclear import. These compounds represent the first in class small molecule inhibitors of HIV-1 nuclear import.
- Published
- 2018
- Full Text
- View/download PDF
3. Y-box-binding protein 1 supports the early and late steps of HIV replication.
- Author
-
Caroline Weydert, Bart van Heertum, Lieve Dirix, Stéphanie De Houwer, Flore De Wit, Jan Mast, Steven J Husson, Katrien Busschots, Renate König, Rik Gijsbers, Jan De Rijck, and Zeger Debyser
- Subjects
Medicine ,Science - Abstract
The human immunodeficiency virus (HIV) depends on cellular proteins, so-called cofactors, to complete its replication cycle. In search for new therapeutic targets we identified the DNA and RNA binding protein Y-box-binding Protein 1 (YB-1) as a cofactor supporting early and late steps of HIV replication. YB-1 depletion resulted in a 10-fold decrease in HIV-1 replication in different cell lines. Dissection of the replication defects revealed that knockdown of YB-1 is associated with a 2- to 5-fold decrease in virion production due to interference with the viral RNA metabolism. Using single-round virus infection experiments we demonstrated that early HIV-1 replication also depends on the cellular YB-1 levels. More precisely, using quantitative PCR and an in vivo nuclear import assay with fluorescently labeled viral particles, we showed that YB-1 knockdown leads to a block between reverse transcription and nuclear import of HIV-1. Interaction studies revealed that YB-1 associates with integrase, although a direct interaction with HIV integrase could not be unambiguously proven. In conclusion, our results indicate that YB-1 affects multiple stages of HIV replication. Future research on the interaction between YB-1 and the virus will reveal whether this protein qualifies as a new antiviral target.
- Published
- 2018
- Full Text
- View/download PDF
4. N-terminal half of transportin SR2 interacts with HIV integrase
- Author
-
Frauke Christ, Zeger Debyser, Jolien Breemans, Sergei V. Strelkov, Vicky G. Tsirkone, Jolien Blokken, Flore De Wit, and Stéphanie De Houwer
- Subjects
Models, Molecular ,Repetitive Sequences, Amino Acid ,inorganic chemicals ,0301 basic medicine ,Anti-HIV Agents ,Protein domain ,Active Transport, Cell Nucleus ,HIV Infections ,HIV Integrase ,Biochemistry ,Protein–protein interaction ,03 medical and health sciences ,Protein Domains ,X-Ray Diffraction ,Humans ,Molecular Biology ,Karyopherin ,Cell Nucleus ,chemistry.chemical_classification ,Genetics ,030102 biochemistry & molecular biology ,biology ,Molecular Bases of Disease ,Cell Biology ,beta Karyopherins ,Integrase ,Cell biology ,030104 developmental biology ,chemistry ,Viral replication ,Drug Design ,RNA splicing ,HIV-1 ,biology.protein ,Beta Karyopherins ,Nuclear transport - Abstract
The karyopherin transportin SR2 (TRN-SR2, TNPO3) is responsible for shuttling specific cargoes such as serine/arginine-rich splicing factors from the cytoplasm to the nucleus. This protein plays a key role in HIV infection by facilitating the nuclear import of the pre-integration complex (PIC) that contains the viral DNA as well as several cellular and HIV proteins, including the integrase. The process of nuclear import is considered to be the bottleneck of the viral replication cycle and therefore represents a promising target for anti-HIV drug design. Previous studies have demonstrated that the direct interaction between TRN-SR2 and HIV integrase predominantly involves the catalytic core domain (CCD) and the C-terminal domain (CTD) of the integrase. We aimed at providing a detailed molecular view of this interaction through a biochemical characterization of the respective protein complex. Size-exclusion chromatography was used to characterize the interaction of TRN-SR2 with a truncated variant of the HIV-1 integrase, including both the CCD and CTD. These experiments indicate that one TRN-SR2 molecule can specifically bind one CCD-CTD dimer. Next, the regions of the solenoid-like TRN-SR2 molecule that are involved in the interaction with integrase were identified using AlphaScreen binding assays, revealing that the integrase interacts with the N-terminal half of TRN-SR2 principally through the HEAT repeats 4, 10, and 11. Combining these results with small-angle X-ray scattering data for the complex of TRN-SR2 with truncated integrase, we propose a molecular model of the complex. We speculate that nuclear import of the PIC may proceed concurrently with the normal nuclear transport. ispartof: Journal of Biological Chemistry vol:292 issue:23 pages:9699-9710 ispartof: location:United States status: published
- Published
- 2017
5. Y-box-binding protein 1 supports the early and late steps of HIV replication
- Author
-
Jan De Rijck, Flore De Wit, Renate König, Lieve Dirix, Jan Mast, Caroline Weydert, Rik Gijsbers, Steven J. Husson, Katrien Busschots, Stéphanie De Houwer, Bart van Heertum, and Zeger Debyser
- Subjects
0301 basic medicine ,RNA viruses ,Small interfering RNA ,Time Factors ,lcsh:Medicine ,RNA-binding protein ,HIV Integrase ,Pathology and Laboratory Medicine ,Virus Replication ,Biochemistry ,chemistry.chemical_compound ,Immunodeficiency Viruses ,STAGE EMBRYONIC-DEVELOPMENT ,Medicine and Health Sciences ,Small interfering RNAs ,lcsh:Science ,IN-VIVO ,GENE-EXPRESSION ,Multidisciplinary ,NUCLEAR EXPRESSION ,VIRAL-RNA ,Cell biology ,Integrase ,Nucleic acids ,Multidisciplinary Sciences ,Medical Microbiology ,Cell Processes ,Viral Pathogens ,Viruses ,HUMAN-IMMUNODEFICIENCY-VIRUS ,293T cells ,Cell lines ,Science & Technology - Other Topics ,RNA, Viral ,Pathogens ,Biological cultures ,MESSENGER-RNA ,Engineering sciences. Technology ,Research Article ,Yellow Fluorescent Protein ,Active Transport, Cell Nucleus ,Biology ,Transfection ,Research and Analysis Methods ,Microbiology ,Virus ,03 medical and health sciences ,Virology ,Retroviruses ,Genetics ,Humans ,Nuclear Import ,Molecular Biology Techniques ,Non-coding RNA ,Microbial Pathogens ,Molecular Biology ,Science & Technology ,Biology and life sciences ,HUMAN-CELLS ,Lentivirus ,lcsh:R ,Organisms ,HIV ,Proteins ,Correction ,Cell Biology ,Reverse Transcription ,Y box binding protein 1 ,Reverse transcriptase ,Viral Replication ,Gene regulation ,Luminescent Proteins ,030104 developmental biology ,Viral replication ,chemistry ,TRANSCRIPTION START SITES ,biology.protein ,HIV-1 ,RNA ,lcsh:Q ,Gene expression ,Y-Box-Binding Protein 1 ,HOST PROTEINS ,DNA ,HeLa Cells - Abstract
The human immunodeficiency virus (HIV) depends on cellular proteins, so-called cofactors, to complete its replication cycle. In search for new therapeutic targets we identified the DNA and RNA binding protein Y-box-binding Protein 1 (YB-1) as a cofactor supporting early and late steps of HIV replication. YB-1 depletion resulted in a 10-fold decrease in HIV-1 replication in different cell lines. Dissection of the replication defects revealed that knockdown of YB-1 is associated with a 2- to 5-fold decrease in virion production due to interference with the viral RNA metabolism. Using single-round virus infection experiments we demonstrated that early HIV-1 replication also depends on the cellular YB-1 levels. More precisely, using quantitative PCR and an in vivo nuclear import assay with fluorescently labeled viral particles, we showed that YB-1 knockdown leads to a block between reverse transcription and nuclear import of HIV-1. Interaction studies revealed that YB-1 associates with integrase, although a direct interaction with HIV integrase could not be unambiguously proven. In conclusion, our results indicate that YB-1 affects multiple stages of HIV replication. Future research on the interaction between YB-1 and the virus will reveal whether this protein qualifies as a new antiviral target. ispartof: PLOS ONE vol:13 issue:7 ispartof: location:United States status: published
- Published
- 2017
6. The HIV-1 Integrase Mutant R263A/K264A Is 2-fold Defective for TRN-SR2 Binding and Viral Nuclear Import
- Author
-
Rik Gijsbers, Lieve Dirix, Wannes Thys, Zeger Debyser, Frauke Christ, Jonas Demeulemeester, Susana Rocha, and Stéphanie De Houwer
- Subjects
Models, Molecular ,inorganic chemicals ,Blotting, Western ,Mutant ,Active Transport, Cell Nucleus ,HIV Integrase ,Virus Replication ,Microbiology ,Binding, Competitive ,Biochemistry ,HIV-1 protease ,Humans ,Molecular Biology ,Karyopherin ,Cell Nucleus ,chemistry.chemical_classification ,Genetics ,Binding Sites ,biology ,virus diseases ,Cell Biology ,beta Karyopherins ,Reverse transcriptase ,Protein Structure, Tertiary ,Integrase ,chemistry ,Viral replication ,Mutation ,HIV-1 ,biology.protein ,Mutant Proteins ,Beta Karyopherins ,Nuclear transport ,HeLa Cells ,Protein Binding - Abstract
Transportin-SR2 (Tnpo3, TRN-SR2), a human karyopherin encoded by the TNPO3 gene, has been identified as a cellular cofactor of HIV-1 replication, specifically interacting with HIV-1 integrase (IN). Whether this interaction mediates the nuclear import of HIV remains controversial. We previously characterized the TRN-SR2 binding interface in IN and introduced mutations at these positions to corroborate the biological relevance of the interaction. The pleiotropic nature of IN mutations complicated the interpretation. Indeed, all previously tested IN interaction mutants also affected RT. Here we report on a virus with a pair of IN mutations, IN(R263A/K264A), that significantly reduce interaction with TRN-SR2. The virus retains wild-type reverse transcription activity but displays a block in nuclear import and integration, as measured by quantitative PCR. The defect in integration of this mutant resulted in a smaller increase in the number of two-long terminal repeat circles than for virus specifically blocked at integration by raltegravir or catalytic site mutations (IN(D64N/D116N/E152Q)). Finally, using an eGFP-IN-labeled HIV fluorescence-based import assay, the defect in nuclear import was corroborated. These data altogether underscore the importance of the HIV-IN TRN-SR2 protein-protein interaction for HIV nuclear import and validate the IN/TRN-SR2 interaction interface as a promising target for future antiviral therapy.
- Published
- 2014
7. Dynamic Oligomerization of Integrase Orchestrates HIV Nuclear Entry
- Author
-
Rik Gijsbers, Stéphanie De Houwer, Jelle Hendrix, Doortje Borrenberghs, Susana Rocha, Frauke Christ, Zeger Debyser, Johan Hofkens, Lieve Dirix, Jolien Blokken, and Flore De Wit
- Subjects
0301 basic medicine ,Active Transport, Cell Nucleus ,HIV Integrase ,Article ,Virus ,Cell Line ,03 medical and health sciences ,Fluorescence Resonance Energy Transfer ,medicine ,Humans ,Nuclear pore ,Cell Nucleus ,Microscopy, Confocal ,Multidisciplinary ,biology ,business.industry ,Chemistry ,Small molecule ,Chromatin ,Integrase ,Cell biology ,030104 developmental biology ,Förster resonance energy transfer ,medicine.anatomical_structure ,Cell culture ,HIV-1 ,Nuclear Pore ,biology.protein ,Intercellular Signaling Peptides and Proteins ,Protein Multimerization ,Telecommunications ,business ,Nucleus ,HeLa Cells - Abstract
Nuclear entry is a selective, dynamic process granting the HIV-1 pre-integration complex (PIC) access to the chromatin. Classical analysis of nuclear entry of heterogeneous viral particles only yields averaged information. We now have employed single-virus fluorescence methods to follow the fate of single viral pre-integration complexes (PICs) during infection by visualizing HIV-1 integrase (IN). Nuclear entry is associated with a reduction in the number of IN molecules in the complexes while the interaction with LEDGF/p75 enhances IN oligomerization in the nucleus. Addition of LEDGINs, small molecule inhibitors of the IN-LEDGF/p75 interaction, during virus production, prematurely stabilizes a higher-order IN multimeric state, resulting in stable IN multimers resistant to a reduction in IN content and defective for nuclear entry. This suggests that a stringent size restriction determines nuclear pore entry. Taken together, this work demonstrates the power of single-virus imaging providing crucial insights in HIV replication and enabling mechanism-of-action studies. We are grateful to Dr. J. Demeulemeester and Dr. J. De Rijck for critical reading and thank P. Van de Velde, B. Vanremoortel and NJ. Van der Veeken for their technical assistance. Viral vector production was performed at the Leuven Viral Vector Core. LEDGINs were synthesized by Cistim/CD3 (courtesy of Dr. A. Marchand). Personal fellowship from 'Agentschap voor Innovatie door Wetenschap en Technologie' [IWT 111595 to D.B.]; Personal fellowship from 'Fonds Wetenschappelijk Onderzoek' [FWO 11M0713N to L.D.]; the Flemish government in the form of long-term structural funding 'Methusalem' [METH/08/04 CASAS], the 'Fonds Wetenschappelijk Onderzoek' [FWO G0B4915]; the KU Leuven Research council [OT/13/098], IWT-SBO-EURECA [HIV-ERA EURECA], the KU Leuven IDO program [IDO/12/008] and the Belgian IAP Belvir.
- Published
- 2016
8. Interaction of Transportin-SR2 with Ras-related Nuclear Protein (Ran) GTPase
- Author
-
Stephen D. Weeks, Oliver Taltynov, Sergei V. Strelkov, Zeger Debyser, Frauke Christ, Stéphanie De Houwer, Vicky G. Tsirkone, Jonas Demeulemeester, and Melanie Gérard
- Subjects
Models, Molecular ,inorganic chemicals ,Active Transport, Cell Nucleus ,HIV Integrase ,Importin ,GTPase ,Biology ,Biochemistry ,Protein–protein interaction ,Humans ,Small GTPase ,Molecular Biology ,Karyopherin ,chemistry.chemical_classification ,Cell Biology ,beta Karyopherins ,Protein Structure, Tertiary ,Cell biology ,ran GTP-Binding Protein ,chemistry ,Multiprotein Complexes ,Protein Structure and Folding ,Ran ,HIV-1 ,Beta Karyopherins ,Protein Multimerization ,Nuclear transport ,Protein Binding - Abstract
The human immunodeficiency virus type 1 (HIV-1) and other lentiviruses are capable of infecting non-dividing cells and therefore need to be imported into the nucleus prior to integration into the host cell chromatin. Transportin-SR2 (TRN-SR2, Transportin-3, TNPO3) is a cellular karyopherin implicated in nuclear import of HIV-1. A model in which TRN-SR2 imports the viral preintegration complex (PIC) into the nucleus is supported by direct interaction between TRN-SR2 and HIV-1 integrase (IN). Residues in the C-terminal domain of HIV-1 IN that mediate binding to TRN-SR2 were recently delineated. As for most nuclear import cargoes, the driving force behind HIV-1 PIC import is likely a gradient of the GDP- and GTP-bound forms of Ran, a small GTPase. In this study we offer biochemical and structural characterization of the interaction between TRN-SR2 and Ran. By size exclusion chromatography we demonstrate stable complex formation of TRN-SR2 and RanGTP in solution. Consistent with the behavior of normal nuclear import cargoes, HIV-1 IN is released from the complex with TRN-SR2 by RanGTP. While in concentrated solutions TRN-SR2 by itself was predominantly present as a dimer, the TRN-SR2-RanGTP complex was significantly more compact. Further analysis supported a model wherein one monomer of TRN-SR2 is bound to one monomer of RanGTP. Finally, we present a homology model of the TRN-SR2-RanGTP complex, which is in excellent agreement with the experimental SAXS data. ispartof: Journal of Biological Chemistry vol:288 issue:35 pages:25603-25613 ispartof: location:United States status: published
- Published
- 2013
9. Identification of Residues in the C-terminal Domain of HIV-1 Integrase That Mediate Binding to the Transportin-SR2 Protein
- Author
-
Zeger Debyser, Katarina Zmajkovicova, Stéphanie De Houwer, Jonas Demeulemeester, Frauke Christ, Oliver Taltynov, and Wannes Thys
- Subjects
inorganic chemicals ,Mutation, Missense ,HIV Integrase ,Biology ,Peptide Mapping ,Microbiology ,Biochemistry ,Protein Structure, Secondary ,SR protein ,Protein structure ,Humans ,Molecular Biology ,Genetics ,chemistry.chemical_classification ,C-terminus ,virus diseases ,Reverse Transcription ,Cell Biology ,beta Karyopherins ,Protein tertiary structure ,Protein Structure, Tertiary ,Integrase ,Amino acid ,Cell biology ,Amino Acid Substitution ,Viral replication ,chemistry ,HIV-1 ,Mutagenesis, Site-Directed ,biology.protein ,Beta Karyopherins ,Peptides ,Protein Binding - Abstract
Transportin-SR2 (TRN-SR2 and TNPO3) is a cellular cofactor of HIV replication that has been implicated in the nuclear import of HIV. TRN-SR2 was originally identified in a yeast two-hybrid screen as an interaction partner of HIV integrase (IN) and in two independent siRNA screens as a cofactor of viral replication. We have now studied the interaction of TRN-SR2 and HIV IN in molecular detail and identified the TRN-SR2 interacting regions of IN. A weak interaction with the catalytic core domain (CCD) and a strong interaction with the C-terminal domain (CTD) of IN were detected. By dissecting the catalytic core domain (CCD) of IN into short structural fragments, we identified a peptide (INIP(1), amino acids (170)EHLKTAVQMAVFIHNFKRKGGI(191)) retaining the ability to interact with TRN-SR2. By dissecting the C-terminal domain (CTD) of IN, we could identify two interacting peptides (amino acids (214)QKQITKIQNFRVYYR(228) and (262)RRKVKIIRDYGK(273)) that come together in the CTD tertiary structure to form an exposed antiparallel β-sheet. Through site-specific mutagenesis, we defined the following sets of amino acids in IN as important for the interaction with TRN-SR2: Phe-185/Lys-186/Arg-187/Lys-188 in the CCD and Arg-262/Arg-263/Lys-264 and Lys-266/Arg-269 in the CTD. An HIV-1 strain carrying K266A/R269A in IN was replication-defective due to a block in reverse transcription, confounding the study of nuclear import. Insight into the IN/TRN-SR2 interaction interface is necessary to guide drug discovery efforts targeting the nuclear entry step of replication.
- Published
- 2012
10. Design of cell-permeable stapled peptides as HIV-1 integrase inhibitors
- Author
-
Zhong Liang Xu, Zeger Debyser, Huiyuan Li, Ya-Qiu Long, Nouri Neamati, Stéphanie De Houwer, Tino W. Sanchez, Frauke Christ, Ying Zhi, Zahrah Zawahir, and Shao Xu Huang
- Subjects
Cell Membrane Permeability ,Cell Survival ,Cell ,Peptide ,HIV Integrase ,Virus Replication ,Cofactor ,Article ,Cell Line, Tumor ,Drug Discovery ,medicine ,Humans ,Amino Acid Sequence ,Enzyme Inhibitors ,Peptide sequence ,Adaptor Proteins, Signal Transducing ,chemistry.chemical_classification ,Microscopy, Confocal ,biology ,Molecular Structure ,Signal transducing adaptor protein ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,HCT116 Cells ,Integrase ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Models, Chemical ,Cell culture ,Drug Design ,Host-Pathogen Interactions ,biology.protein ,Hiv 1 integrase ,Biocatalysis ,HIV-1 ,Molecular Medicine ,Peptides ,Protein Binding ,Transcription Factors - Abstract
HIV-1 integrase (IN) catalyzes the integration of viral DNA into the host genome, involving several interactions with host proteins. We have previously identified peptide IN inhibitors derived from the alpha-helical regions along the dimeric interface of HIV-1 IN. Herein, we show that appropriate hydrocarbon-stapling of these peptides to stabilize their helical structure remarkably improves the cell permeability, thus allowing inhibition of the HIV-1 replication in cell culture. Furthermore, the stabilized peptides inhibit the interaction of IN with the cellular cofactor LEDGF/p75. Cellular uptake of the stapled peptide was confirmed in four different cell lines using a fluorescein-labeled analogue. Given their enhanced potency and cell permeability, these stapled peptides can serve as not only lead compounds of novel HIV-1 IN inhibitors but also prototypical biochemical probes or ‘nanoneedles’ for the elucidation of HIV-1 IN dimerization and host co-factor interactions within their native cellular environment.
- Published
- 2013
11. Interplay between HIV entry and transportin-SR2 dependency
- Author
-
Oliver Taltynov, Frauke Christ, Rik Gijsbers, Wannes Thys, Melanie Gérard, Stéphanie De Houwer, Zeger Debyser, Jan De Rijck, Renée Vancraenenbroeck, and Jonas Demeulemeester
- Subjects
lcsh:Immunologic diseases. Allergy ,inorganic chemicals ,Feline immunodeficiency virus ,viruses ,Viral transformation ,Virus ,Cell Line ,03 medical and health sciences ,Virology ,Murine leukemia virus ,Humans ,030304 developmental biology ,0303 health sciences ,biology ,Research ,030302 biochemistry & molecular biology ,Virus Internalization ,biology.organism_classification ,beta Karyopherins ,3. Good health ,Integrase ,Infectious Diseases ,Capsid ,biology.protein ,HIV-1 ,Beta Karyopherins ,lcsh:RC581-607 ,Oncovirus - Abstract
Background Transportin-SR2 (TRN-SR2, TNPO3, transportin 3) was previously identified as an interaction partner of human immunodeficiency virus type 1 (HIV-1) integrase and functions as a nuclear import factor of HIV-1. A possible role of capsid in transportin-SR2-mediated nuclear import was recently suggested by the findings that a chimeric HIV virus, carrying the murine leukemia virus (MLV) capsid and matrix proteins, displayed a transportin-SR2 independent phenotype, and that the HIV-1 N74D capsid mutant proved insensitive to transportin-SR2 knockdown. Results Our present analysis of viral specificity reveals that TRN-SR2 is not used to the same extent by all lentiviruses. The DNA flap does not determine the TRN-SR2 requirement of HIV-1. We corroborate the TRN-SR2 independent phenotype of the chimeric HIV virus carrying the MLV capsid and matrix proteins. We reanalyzed the HIV-1 N74D capsid mutant in cells transiently or stably depleted of transportin-SR2 and confirm that the N74D capsid mutant is independent of TRN-SR2 when pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G). Remarkably, although somewhat less dependent on TRN-SR2 than wild type virus, the N74D capsid mutant carrying the wild type HIV-1 envelope required TRN-SR2 for efficient replication. By pseudotyping with envelopes that mediate pH-independent viral uptake including HIV-1, measles virus and amphotropic MLV envelopes, we demonstrate that HIV-1 N74D capsid mutant viruses retain partial dependency on TRN-SR2. However, this dependency on TRN-SR2 is lost when the HIV N74D capsid mutant is pseudotyped with envelopes mediating pH-dependent endocytosis, such as the VSV-G and Ebola virus envelopes. Conclusion Here we discover a link between the viral entry of HIV and its interaction with TRN-SR2. Our data confirm the importance of TRN-SR2 in HIV-1 replication and argue for careful interpretation of experiments performed with VSV-G pseudotyped viruses in studies on early steps of HIV replication including the role of capsid therein.
- Published
- 2010
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.