LIVIVO - Search results -

Search results

Result 1 - 10 of total 52

Search options

Article ; Online: Interview with a Retrovirologist: Sebla B. Kutluay in conversation with Carol Carter.

Carter, Carol / Kutluay, Sebla B

Retrovirology

2021 Volume 18, Issue 1, Page(s) 18

MeSH term(s)	Female ; Humans ; Interviews as Topic ; Laboratory Personnel ; Research ; Retroviridae
Language	English
Publishing date	2021-07-01
Publishing country	England
Document type	Interview
ISSN	1742-4690
ISSN (online)	1742-4690
DOI	10.1186/s12977-021-00562-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Going beyond Integration: The Emerging Role of HIV-1 Integrase in Virion Morphogenesis.

Elliott, Jennifer L / Kutluay, Sebla B

Viruses

2020 Volume 12, Issue 9

Abstract: The HIV-1 integrase enzyme (IN) plays a critical role in the viral life cycle by integrating the reverse-transcribed viral DNA into the host chromosome. This function of IN has been well studied, and the knowledge gained has informed the design of small ... ...

Abstract	The HIV-1 integrase enzyme (IN) plays a critical role in the viral life cycle by integrating the reverse-transcribed viral DNA into the host chromosome. This function of IN has been well studied, and the knowledge gained has informed the design of small molecule inhibitors that now form key components of antiretroviral therapy regimens. Recent discoveries unveiled that IN has an under-studied yet equally vital second function in human immunodeficiency virus type 1 (HIV-1) replication. This involves IN binding to the viral RNA genome in virions, which is necessary for proper virion maturation and morphogenesis. Inhibition of IN binding to the viral RNA genome results in mislocalization of the viral genome inside the virus particle, and its premature exposure and degradation in target cells. The roles of IN in integration and virion morphogenesis share a number of common elements, including interaction with viral nucleic acids and assembly of higher-order IN multimers. Herein we describe these two functions of IN within the context of the HIV-1 life cycle, how IN binding to the viral genome is coordinated by the major structural protein, Gag, and discuss the value of targeting the second role of IN in virion morphogenesis.
MeSH term(s)	Animals ; HIV Infections/virology ; HIV Integrase/genetics ; HIV Integrase/metabolism ; HIV-1/enzymology ; HIV-1/genetics ; HIV-1/growth & development ; HIV-1/physiology ; Humans ; Virion/enzymology ; Virion/genetics ; Virion/growth & development ; Virion/physiology ; Virus Integration
Chemical Substances	HIV Integrase (EC 2.7.7.-) ; p31 integrase protein, Human immunodeficiency virus 1 (YY6481J2FF)
Language	English
Publishing date	2020-09-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12091005
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Calpain-2 mediates SARS-CoV-2 entry via regulating ACE2 levels.

Zeng, Qiru / Antia, Avan / Casorla-Perez, Luis Alberto / Puray-Chavez, Maritza / Kutluay, Sebla B / Ciorba, Matthew A / Ding, Siyuan

mBio

2024 Volume 15, Issue 3, Page(s) e0228723

Abstract: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, much effort has been dedicated to identifying effective antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A number of calpain inhibitors show ... ...

Abstract	Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, much effort has been dedicated to identifying effective antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A number of calpain inhibitors show excellent antiviral activities against SARS-CoV-2 by targeting the viral main protease (M Importance: Many efforts in small-molecule screens have been made to counter SARS-CoV-2 infection by targeting the viral main protease, the major element that processes viral proteins after translation. Here, we discovered that calpain inhibitors further block SARS-CoV-2 infection in a main protease-independent manner. We identified the host cysteine protease calpain-2 as an important positive regulator of the cell surface levels of SARS-CoV-2 cellular receptor ACE2 and, thus, a facilitator of viral infection. By either pharmacological inhibition or genetic knockout of calpain-2, the SARS-CoV-2 binding to host cells is blocked and viral infection is decreased. Our findings highlight a novel mechanism of ACE2 regulation, which presents a potential new therapeutic target. Since calpain inhibitors also potently interfere with the viral main protease, our data also provide a mechanistic understanding of the potential use of calpain inhibitors as dual inhibitors (entry and replication) in the clinical setting of COVID-19 diseases. Our findings bring mechanistic insights into the cellular process of SARS-CoV-2 entry and offer a novel explanation to the mechanism of activities of calpain inhibitors.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19 ; Calpain/metabolism ; Calpain/pharmacology ; Angiotensin-Converting Enzyme 2/metabolism ; Spike Glycoprotein, Coronavirus/metabolism ; Antiviral Agents/pharmacology ; Virus Internalization
Chemical Substances	spike protein, SARS-CoV-2 ; Calpain (EC 3.4.22.-) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Spike Glycoprotein, Coronavirus ; Antiviral Agents
Language	English
Publishing date	2024-02-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.02287-23
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: HIV-1 capsid stability and reverse transcription are finely balanced to minimize sensing of reverse transcription products

Eschbach, Jenna E / Puray-Chavez, Maritza / Mohammed, Shawn / Wang, Qiankun / Xia, Ming / Huang, Lin-Chen / Shan, Liang / Kutluay, Sebla B

mBio

2024 , Page(s) e0034824

Abstract: A critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms the conical core when it rearranges around the dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune ... ...

Abstract	A critical determinant for early post-entry events, the HIV-1 capsid (CA) protein forms the conical core when it rearranges around the dimeric RNA genome and associated viral proteins. Although mutations in CA have been reported to alter innate immune sensing of HIV-1, a direct link between core stability and sensing of HIV-1 nucleic acids has not been established. Herein, we assessed how manipulating the stability of the CA lattice through chemical and genetic approaches affects innate immune recognition of HIV-1. We found that destabilization of the CA lattice resulted in potent sensing of reverse transcription products when destabilization Importance: In HIV-1 particles, the dimeric RNA genome and associated viral proteins and enzymes are encased in a proteinaceous lattice composed of the viral capsid protein. Herein, we assessed how altering the stability of this capsid lattice through orthogonal genetic and chemical approaches impacts the induction of innate immune responses. Specifically, we found that decreasing capsid lattice stability results in more potent sensing of viral reverse transcription products, but not the genomic RNA, in a cGAS-STING-dependent manner. The recently developed capsid inhibitors lenacapavir and GS-CA1 enhanced the innate immune sensing of HIV-1. Unexpectedly, due to increased levels of reverse transcription and cytosolic accumulation of the resulting viral cDNA, capsid mutants with hyperstable cores also resulted in the potent induction of type I interferon-mediated innate immunity. Our findings suggest that HIV-1 capsid lattice stability and reverse transcription are finely balanced to minimize exposure of reverse transcription products in the cytosol of host cells.
Language	English
Publishing date	2024-03-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.00348-24
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: CLIP-related methodologies and their application to retrovirology.

Bieniasz, Paul D / Kutluay, Sebla B

Retrovirology

2018 Volume 15, Issue 1, Page(s) 35

Abstract: Virtually every step of HIV-1 replication and numerous cellular antiviral defense mechanisms are regulated by the binding of a viral or cellular RNA-binding protein (RBP) to distinct sequence or structural elements on HIV-1 RNAs. Until recently, these ... ...

Abstract	Virtually every step of HIV-1 replication and numerous cellular antiviral defense mechanisms are regulated by the binding of a viral or cellular RNA-binding protein (RBP) to distinct sequence or structural elements on HIV-1 RNAs. Until recently, these protein-RNA interactions were studied largely by in vitro binding assays complemented with genetics approaches. However, these methods are highly limited in the identification of the relevant targets of RBPs in physiologically relevant settings. Development of crosslinking-immunoprecipitation sequencing (CLIP) methodology has revolutionized the analysis of protein-nucleic acid complexes. CLIP combines immunoprecipitation of covalently crosslinked protein-RNA complexes with high-throughput sequencing, providing a global account of RNA sequences bound by a RBP of interest in cells (or virions) at near-nucleotide resolution. Numerous variants of the CLIP protocol have recently been developed, some with major improvements over the original. Herein, we briefly review these methodologies and give examples of how CLIP has been successfully applied to retrovirology research.
MeSH term(s)	Animals ; Binding Sites ; Genome, Viral ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions ; Humans ; Immunoprecipitation/methods ; Protein Binding ; RNA, Viral/genetics ; RNA, Viral/metabolism ; RNA-Binding Proteins/metabolism ; Retroviridae/physiology ; Retroviridae Infections/virology ; Virus Replication
Chemical Substances	RNA, Viral ; RNA-Binding Proteins
Language	English
Publishing date	2018-05-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2142602-8
ISSN	1742-4690 ; 1742-4690
ISSN (online)	1742-4690
ISSN	1742-4690
DOI	10.1186/s12977-018-0417-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Going beyond Integration: The Emerging Role of HIV-1 Integrase in Virion Morphogenesis

Elliott, Jennifer L / Kutluay, Sebla B

Viruses. 2020 Sept. 09, v. 12, no. 9

2020

Abstract	The HIV-1 integrase enzyme (IN) plays a critical role in the viral life cycle by integrating the reverse-transcribed viral DNA into the host chromosome. This function of IN has been well studied, and the knowledge gained has informed the design of small molecule inhibitors that now form key components of antiretroviral therapy regimens. Recent discoveries unveiled that IN has an under-studied yet equally vital second function in human immunodeficiency virus type 1 (HIV-1) replication. This involves IN binding to the viral RNA genome in virions, which is necessary for proper virion maturation and morphogenesis. Inhibition of IN binding to the viral RNA genome results in mislocalization of the viral genome inside the virus particle, and its premature exposure and degradation in target cells. The roles of IN in integration and virion morphogenesis share a number of common elements, including interaction with viral nucleic acids and assembly of higher-order IN multimers. Herein we describe these two functions of IN within the context of the HIV-1 life cycle, how IN binding to the viral genome is coordinated by the major structural protein, Gag, and discuss the value of targeting the second role of IN in virion morphogenesis.
Keywords	DNA ; Human immunodeficiency virus 1 ; RNA ; antiretroviral agents ; chromosomes ; genome ; integrases ; morphogenesis ; structural proteins ; therapeutics ; virion
Language	English
Dates of publication	2020-0909
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v12091005
Database	NAL-Catalogue (AGRICOLA)

Order via subito

Article: Calpain-2 mediates SARS-CoV-2 entry and represents a therapeutic target.

Zeng, Qiru / Antia, Avan / Puray-Chavez, Maritza / Kutluay, Sebla B / Ding, Siyuan

bioRxiv : the preprint server for biology

2022

Abstract	Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, much effort has been dedicated to identifying effective antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A number of calpain inhibitors show excellent antiviral activities against SARS-CoV-2 by targeting the viral main protease (M
Language	English
Publishing date	2022-11-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.11.29.518418
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article: A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models.

Puray-Chavez, Maritza / LaPak, Kyle M / Jasuja, Ria / Pan, Jiehong / Xu, Jian / Eschbach, Jenna E / Mohammed, Shawn / Lawson, Dana Q / Wang, Qibo / Brody, Steven L / Major, Michael B / Goldfarb, Dennis / Kutluay, Sebla B

bioRxiv : the preprint server for biology

2024

Abstract: Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. From a screen of human airway derived cell lines that express varying levels of ACE2/TMPRSS2, we found a subset that express comparably high ... ...

Abstract	Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. From a screen of human airway derived cell lines that express varying levels of ACE2/TMPRSS2, we found a subset that express comparably high endogenous levels of ACE2 but surprisingly did not support SARS-CoV-2 replication. Here we report that this resistance is mediated by a basally active cGAS-STING pathway culminating in interferon (IFN)-mediated restriction of SARS-CoV-2 replication at a post-entry step. Pharmacological inhibition of JAK1/2, depletion of the IFN-α receptor and cGAS-STING pathway effectors substantially increased SARS-CoV-2 replication in these cell models. While depletion of cGAS or STING was sufficient to reduce the preexisting levels of IFN-stimulated genes (ISGs), SARS-CoV-2 infection in STING knockout cells independently induced ISG expression. Remarkably, SARS-CoV-2-induced ISG expression in STING knockout cell as well as in primary human airway cultures was limited to uninfected bystander cells, demonstrating efficient antagonism of the type I/III IFN-pathway, but not viral sensing or IFN production, in productively infected cells. Of note, SARS-CoV-2-infected primary human airway cells also displayed markedly lower levels of STING expression, raising the possibility that SARS-CoV-2 can target STING expression or preferentially infect cells that express low levels of STING. Finally, ectopic ACE2 overexpression overcame the IFN-mediated blocks, suggesting the ability of SARS-CoV-2 to overcome these possibly saturable blocks to infection. Our study highlights that in addition to viral receptors, basal activation of the cGAS-STING pathway and innate immune defenses may contribute to defining SARS-CoV-2 cellular tropism.
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.07.574522
Database	MEDical Literature Analysis and Retrieval System OnLINE

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: Clip for studying protein-RNA interactions that regulate virus replication.

Shema Mugisha, Christian / Tenneti, Kasyap / Kutluay, Sebla B

Methods (San Diego, Calif.)

2019 Volume 183, Page(s) 84–92

Abstract: Viral and cellular RNA-binding proteins regulate numerous key steps in the replication of diverse virus genera. Viruses efficiently co-opt the host cell machinery for purposes such as transcription, splicing and subcellular localization of viral genomes. ...

Abstract	Viral and cellular RNA-binding proteins regulate numerous key steps in the replication of diverse virus genera. Viruses efficiently co-opt the host cell machinery for purposes such as transcription, splicing and subcellular localization of viral genomes. Though viral RNAs often need to resemble cellular RNAs to effectively utilize the cellular machinery, they still retain unique sequence and structural features for recognition by viral proteins for processes such as RNA polymerization, RNA export and selective packaging into virus particles. While beneficial for virus replication, distinct features of viral nucleic acids can also be recognized as foreign by several host defense proteins. Development of the crosslinking immunoprecipitation coupled with sequencing (CLIP) approach has allowed the study of viral and cellular RNA binding proteins that regulate critical aspects of viral replication in unprecedented detail. By combining immunoprecipitation of covalently crosslinked protein-RNA complexes with high-throughput sequencing, CLIP provides a global account of RNA sequences bound by RNA-binding proteins of interest in physiological settings and at near-nucleotide resolution. Here, we describe the step-by-step application of the CLIP methodology within the context of two cellular splicing regulatory proteins, hnRNP A1 and hnRNP H1 that regulate HIV-1 splicing. In principle, this versatile protocol can be applied to many other viral and cellular RNA-binding proteins.
MeSH term(s)	Chromatin Immunoprecipitation Sequencing/methods ; HEK293 Cells ; HIV-1/genetics ; Heterogeneous Nuclear Ribonucleoprotein A1/genetics ; Heterogeneous Nuclear Ribonucleoprotein A1/metabolism ; Heterogeneous-Nuclear Ribonucleoprotein Group F-H/genetics ; Heterogeneous-Nuclear Ribonucleoprotein Group F-H/metabolism ; Humans ; RNA Splicing ; RNA, Viral/genetics ; RNA, Viral/metabolism ; Virus Replication
Chemical Substances	Heterogeneous Nuclear Ribonucleoprotein A1 ; Heterogeneous-Nuclear Ribonucleoprotein Group F-H ; RNA, Viral
Language	English
Publishing date	2019-11-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1066584-5
ISSN	1095-9130 ; 1046-2023
ISSN (online)	1095-9130
ISSN	1046-2023
DOI	10.1016/j.ymeth.2019.11.011
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3239: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Analysis of HIV-1 Gag-RNA Interactions in Cells and Virions by CLIP-seq.

Kutluay, Sebla B / Bieniasz, Paul D

Methods in molecular biology (Clifton, N.J.)

2015 Volume 1354, Page(s) 119–131

Abstract: Next-generation sequencing-based methodologies have revolutionized the analysis of protein-nucleic acid complexes; yet these novel approaches have rarely been applied in virology. Because it has an RNA genome, RNA-protein interactions play critical roles ...

Abstract	Next-generation sequencing-based methodologies have revolutionized the analysis of protein-nucleic acid complexes; yet these novel approaches have rarely been applied in virology. Because it has an RNA genome, RNA-protein interactions play critical roles in human immunodeficiency virus type 1 (HIV-1) replication. In many cases, the binding sites of proteins on HIV-1 RNA molecules in physiologically relevant settings are not known. Cross-linking-immunoprecipitation sequencing (CLIP-seq) methodologies, which combine immunoprecipitation of covalently crosslinked protein-RNA complexes with high-throughput sequencing, is a powerful technique that can be applied to such questions as it provides a global account of RNA sequences bound by a RNA-binding protein of interest in physiological settings at near-nucleotide resolution. Here, we describe the application of the CLIP-seq methodology to identify the RNA molecules that are bound by the HIV-1 Gag protein in cells and in virions. This protocol can easily be applied to other viral and cellular RNA-binding proteins that influence HIV-1 replication.
MeSH term(s)	Base Sequence ; Binding Sites ; Gene Products, gag/metabolism ; Genomics/methods ; HIV Infections/metabolism ; HIV Infections/virology ; HIV-1/genetics ; HIV-1/metabolism ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Immunoprecipitation/methods ; Protein Binding ; RNA, Viral/genetics ; RNA, Viral/metabolism ; RNA-Binding Proteins/metabolism ; Reverse Transcriptase Polymerase Chain Reaction/methods ; Ultraviolet Rays ; Virion/genetics ; Virion/metabolism
Chemical Substances	Gene Products, gag ; RNA, Viral ; RNA-Binding Proteins
Language	English
Publishing date	2015-12-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-3046-3_8
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- Full text online
- Order with fees

To top

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Order via subito

Inter-library loan at ZB MED