HIV-1 Nef and host cell protein kinases

10.2741/a217 ◽  
1997 ◽  
Vol 2 (4) ◽  
pp. d606-618 ◽  
Author(s):  
Kalle Saksela
Keyword(s):  
Host Cell ◽  
Protein Kinases ◽  
Cell Protein ◽  
Host Cell Protein ◽  
Hiv 1

scholarly journals HIV-1 Subtype C with PYxE Insertion Has Enhanced Binding of Gag-p6 to Host Cell Protein ALIX and Increased Replication Fitness

2019 ◽  
Vol 93 (9) ◽  
Author(s):  
Robert van Domselaar ◽  
Duncan T. Njenda ◽  
Rohit Rao ◽  
Anders Sönnerborg ◽  
Kamalendra Singh ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Protein ◽  
Host Cell Protein ◽  
Subtype C ◽  
Viral Growth ◽  
Viral Budding ◽  
Motif Site ◽  
Tenofovir Alafenamide ◽  
Replication Fitness ◽  
Hiv 1

ABSTRACTHuman immunodeficiency virus type 1 subtype C (HIV-1C) has a natural deletion of a YPxL motif in its Gag-p6 late domain. This domain mediates the binding of Gag to host cell protein ALIX and subsequently facilitates viral budding. In a subset of HIV-1C-infected individuals, the tetrapeptide insertion PYxE has been identified at the deleted YPxL motif site. Here, we report the consequences of PYxE insertion on the interaction with ALIX and the relevance regarding replication fitness and drug sensitivity. In our three HIV-1C cohorts, PYKE and PYQE were most prevalent among PYxE variants. Throughin silicopredictions andin vitroexperiments, we showed that HIV-1C Gag has an increased binding to ALIX when the PYxE motif is present. To go more into the clinical relevance of the PYxE insertion, we obtained patient-derivedgag-polsequences from HIV-1CPYxEiviruses and inserted them in a reference HIV-1 sequence. Viral growth was increased, and the sensitivity to the protease inhibitor (PI) lopinavir (LPV) and nucleoside reverse transcriptase inhibitor tenofovir alafenamide (TAF) was decreased for some of the HIV-1C PYxE variants compared to that of wild-type variants. Our data suggest that PYxE insertion in Gag restores the ability of Gag to bind ALIX and correlates with enhanced viral fitness in the absence or presence of LPV and TAF. The high prevalence and increased replication fitness of the HIV-1C virus with PYxE insertion indicates the clinical importance of these viral variants.IMPORTANCEGenomic differences within HIV-1 subtypes is associated with various degrees of viral spread, disease progression, and clinical outcome. Viral budding is essential in the HIV-1 life cycle and mainly mediated through the interaction of Gag with host proteins. Two motifs within Gag-p6 mediate binding of host cell proteins and facilitate budding. HIV-1C has a natural deletion of one of these two motifs, resulting in an inability to bind to host cell protein ALIX. Previously, we have identified a tetrapeptide (PYxE) insertion at this deleted motif site in a subset of HIV-1C patients. Here, we report the incidence of PYxE insertions in three different HIV-1C cohorts, and the insertion restores the binding of Gag to ALIX. It also increases viral growth even in the presence of the antiretroviral drugs lopinavir and tenofovir alafenamide. Hence, PYxE insertion in HIV-1C might be biologically relevant for viruses and clinically significant among patients.

scholarly journals Differential upregulation of host cell protein kinases by the replication of α-, β- and γ-herpesviruses provides a signature of virus-specific signalling

2020 ◽  
Vol 101 (3) ◽  
pp. 284-289 ◽  
Author(s):  
Manfred Marschall ◽  
Hanife Strojan ◽  
Richard Kiener ◽  
Christina Wangen ◽  
Eric Sonntag ◽  
...  
Keyword(s):  
Host Cell ◽  
Protein Kinases ◽  
Cell Protein ◽  
Host Cell Protein

scholarly journals HIV-1 subtype C with PYxE insertion has enhanced binding of Gag-p6 to host cell protein ALIX and increased replication fitness

2018 ◽  
Author(s):  
Robert van Domselaar ◽  
Duncan T. Njenda ◽  
Rohit Rao ◽  
Anders Sönnerborg ◽  
Kamalendra Singh ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Protein ◽  
Host Cell Protein ◽  
Subtype C ◽  
Viral Growth ◽  
Viral Budding ◽  
Motif Site ◽  
Tenofovir Alafenamide ◽  
Replication Fitness ◽  
Hiv 1

AbstractHuman immunodeficiency virus type 1 subtype C (HIV-1C) has a natural deletion of a YPxL motif in its Gag-p6 late domain. This domain mediates the binding of Gag to host cell protein ALIX and subsequently facilitates viral budding. In a subset of HIV-1C infected individuals, the tetrapeptide insertion PYxE has been identified at the deleted YPxL motif site. Here, we report the consequences of PYxE insertion on the interaction with ALIX and the relevance regarding replication fitness and drug sensitivity. In our three HIV-1C cohorts, PYKE and PYQE were most prevalent among PYxE variants. Throughin silicopredictions andin vitroexperiments, we showed that HIV-1C Gag has an increased binding to ALIX when PYxE motif is present. To go more into the clinical relevance of the PYxE insertion, we obtained patient-derived gag-pol sequences from HIV-1CPYxEiviruses and inserted them in a reference HIV-1. Viral growth was increased, and the sensitivity to protease inhibitor (PI) lopinavir (LPV) and nucleoside reverse transcriptase inhibitor tenofovir alafenamide (TAF) was decreased for some of the HIV-1C PYxE variants compared to wild-type variants. Our data suggest that PYxE insertion in Gag restores the ability of Gag to bind ALIX and correlates with enhanced viral fitness in the absence or presence of LPV and TAF. The high prevalence and increased replication fitness of the HIV-1C virus with PYxE insertion could indicate the clinical importance of these viral variants.ImportanceGenomic differences within HIV-1 subtypes is associated with a varying degree of viral spread, disease progression, and clinical outcome. Viral budding is essential in the HIV-1 life cycle and mainly mediated through the interaction of Gag with host proteins. Two motifs within Gag-p6 mediate binding of host cell proteins and facilitate budding. HIV-1 subtype C (HIV-1C) has a natural deletion of one of these two motifs resulting in an inability to bind to host cell protein ALIX. Previously, we have identified a tetrapeptide (PYxE) insertion at this deleted motif site in a subset of HIV-1C patients. Here, we report the incidence of PYxE insertions in three different HIV-1C cohorts, and the insertion restores the binding of Gag to ALIX. It also increases viral growth even in the presence of antiretroviral drugs lopinavir and tenofovir alafenamide. Hence, PYxE insertion in HIV-1C might be biologically relevant for viruses and clinically significant among patients.

scholarly journals Shigella flexneri-HeLa cell interactions: A putative role for host cell protein kinases

1995 ◽  
Vol 10 (2) ◽  
pp. 93-100 ◽  
Author(s):  
Christopher Collaco ◽  
Roy B. Dyer ◽  
Richard Doan ◽  
Norbert K. Herzog ◽  
David W. Niesel
Keyword(s):  
Hela Cell ◽  
Host Cell ◽  
Protein Kinases ◽  
Shigella Flexneri ◽  
Cell Interactions ◽  
Cell Protein ◽  
Host Cell Protein ◽  
Putative Role

scholarly journals The Campylobacter jejuni CiaD effector co-opts the host cell protein IQGAP1 to promote cell entry

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nicholas M. Negretti ◽  
Christopher R. Gourley ◽  
Prabhat K. Talukdar ◽  
Geremy Clair ◽  
Courtney M. Klappenbach ◽  
...  
Keyword(s):  
Host Cell ◽  
Campylobacter Jejuni ◽  
Foodborne Pathogen ◽  
Small Gtpase ◽  
Host Cells ◽  
Cell Protein ◽  
Host Cell Protein ◽  
Cell Binding ◽  
Actin Reorganization ◽  
Cell Cytosol

AbstractCampylobacter jejuni is a foodborne pathogen that binds to and invades the epithelial cells lining the human intestinal tract. Maximal invasion of host cells by C. jejuni requires cell binding as well as delivery of the Cia proteins (Campylobacter invasion antigens) to the host cell cytosol via the flagellum. Here, we show that CiaD binds to the host cell protein IQGAP1 (a Ras GTPase-activating-like protein), thus displacing RacGAP1 from the IQGAP1 complex. This, in turn, leads to the unconstrained activity of the small GTPase Rac1, which is known to have roles in actin reorganization and internalization of C. jejuni. Our results represent the identification of a host cell protein targeted by a flagellar secreted effector protein and demonstrate that C. jejuni-stimulated Rac signaling is dependent on IQGAP1.

Evaluating Immunogenicity Risk Due to Host Cell Protein Impurities in Antibody-Based Biotherapeutics

2016 ◽  
Vol 18 (6) ◽  
pp. 1439-1452 ◽  
Author(s):  
Vibha Jawa ◽  
Marisa K. Joubert ◽  
Qingchun Zhang ◽  
Meghana Deshpande ◽  
Suminda Hapuarachchi ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Protein ◽  
Host Cell Protein
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