scholarly journals A Genome-Wide siRNA Screen to Identify Host Factors Necessary for Growth of the Parasite Toxoplasma gondii

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e68129 ◽  
Author(s):  
Lindsey A. Moser ◽  
Angela M. Pollard ◽  
Laura J. Knoll
Keyword(s):  
Toxoplasma Gondii ◽  
Host Factors ◽  
Sirna Screen ◽  
Genome Wide ◽  
A Genome

scholarly journals A Genome-Wide siRNA Screen Implicates Spire1/2 in SipA-Driven Salmonella Typhimurium Host Cell Invasion

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0161965 ◽  
Author(s):  
Daniel Andritschke ◽  
Sabrina Dilling ◽  
Mario Emmenlauer ◽  
Tobias Welz ◽  
Fabian Schmich ◽  
...  
Keyword(s):  
Salmonella Typhimurium ◽  
Host Cell ◽  
Cell Invasion ◽  
Host Cell Invasion ◽  
Sirna Screen ◽  
Genome Wide ◽  
A Genome

scholarly journals A genome-wide CRISPR screen identifies UFMylation and TRAMP-like complexes as host factors required for hepatitis A virus infection

Cell Reports ◽  
2021 ◽  
Vol 34 (11) ◽  
pp. 108859
Author(s):  
Jessie Kulsuptrakul ◽  
Ruofan Wang ◽  
Nathan L. Meyers ◽  
Melanie Ott ◽  
Andreas S. Puschnik
Keyword(s):  
Virus Infection ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Host Factors ◽  
Genome Wide ◽  
A Genome ◽  
Crispr Screen

scholarly journals Yersinia pestis Targets the Host Endosome Recycling Pathway during the Biogenesis of the Yersinia-Containing Vacuole To Avoid Killing by Macrophages

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Michael G. Connor ◽  
Amanda R. Pulsifer ◽  
Donghoon Chung ◽  
Eric C. Rouchka ◽  
Brian K. Ceresa ◽  
...  
Keyword(s):  
Yersinia Pestis ◽  
Host Factors ◽  
Endocytic Recycling ◽  
Recycling Endosome ◽  
Independent Manner ◽  
Genome Wide ◽  
Type Three Secretion System ◽  
A Genome ◽  
Recycling Pathway ◽  
Bacterial Replication

ABSTRACTYersinia pestishas evolved many strategies to evade the innate immune system. One of these strategies is the ability to survive within macrophages. Upon phagocytosis,Y. pestisprevents phagolysosome maturation and establishes a modified compartment termed theYersinia-containing vacuole (YCV).Y. pestisactively inhibits the acidification of this compartment, and eventually, the YCV transitions from a tight-fitting vacuole into a spacious replicative vacuole. The mechanisms to generate the YCV have not been defined. However, we hypothesized that YCV biogenesis requiresY. pestisinteractions with specific host factors to subvert normal vesicular trafficking. In order to identify these factors, we performed a genome-wide RNA interference (RNAi) screen to identify host factors required forY. pestissurvival in macrophages. This screen revealed that 71 host proteins are required for intracellular survival ofY. pestis. Of particular interest was the enrichment for genes involved in endosome recycling. Moreover, we demonstrated thatY. pestisactively recruits Rab4a and Rab11b to the YCV in a type three secretion system-independent manner, indicating remodeling of the YCV byY. pestisto resemble a recycling endosome. While recruitment of Rab4a was necessary to inhibit YCV acidification and lysosomal fusion early during infection, Rab11b appeared to contribute to later stages of YCV biogenesis. We also discovered thatY. pestisdisrupts global host endocytic recycling in macrophages, possibly through sequestration of Rab11b, and this process is required for bacterial replication. These data provide the first evidence thatY. pestistargets the host endocytic recycling pathway to avoid phagolysosomal maturation and generate the YCV.IMPORTANCEYersinia pestiscan infect and survive within macrophages. However, the mechanisms that the bacterium use to subvert killing by these phagocytes have not been defined. To provide a better understanding of these mechanisms, we used an RNAi approach to identify host factors required for intracellularY. pestissurvival. This approach revealed that the host endocytic recycling pathway is essential forY. pestisto avoid clearance by the macrophage. We further demonstrate thatY. pestisremodels the phagosome to resemble a recycling endosome, allowing the bacterium to avoid the normal phagolysosomal maturation pathway. Moreover, we show that infection withY. pestisdisrupts normal recycling in the macrophage and that disruption is required for bacterial replication. These findings provide the first evidence thatY. pestistargets the host endocytic recycling pathway in order to evade killing by macrophages.

scholarly journals A Genome-wide siRNA Screen Identifies Proteasome Addiction as a Vulnerability of Basal-like Triple-Negative Breast Cancer Cells

Cancer Cell ◽  
2013 ◽  
Vol 24 (2) ◽  
pp. 182-196 ◽  
Author(s):  
Fabio Petrocca ◽  
Gabriel Altschuler ◽  
Shen Mynn Tan ◽  
Marc L. Mendillo ◽  
Haoheng Yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Sirna Screen ◽  
Genome Wide ◽  
A Genome

scholarly journals A Genome-Wide siRNA Screen Reveals Multiple mTORC1 Independent Signaling Pathways Regulating Autophagy under Normal Nutritional Conditions

2010 ◽  
Vol 18 (6) ◽  
pp. 1041-1052 ◽  
Author(s):  
Marta M. Lipinski ◽  
Greg Hoffman ◽  
Aylwin Ng ◽  
Wen Zhou ◽  
Bénédicte F. Py ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Sirna Screen ◽  
Nutritional Conditions ◽  
Genome Wide ◽  
A Genome

scholarly journals A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets

PLoS Biology ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. e3001490
Author(s):  
Annika Kratzel ◽  
Jenna N. Kelly ◽  
Philip V’kovski ◽  
Jasmine Portmann ◽  
Yannick Brüggemann ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Huh7 Cell ◽  
Host Factors ◽  
Genome Wide ◽  
A Genome ◽  
Dependent Inhibition ◽  
Crispr Screen ◽  
Human Coronaviruses ◽  
Approved Drugs ◽  
Huh7 Cell Line

Over the past 20 years, 3 highly pathogenic human coronaviruses (HCoVs) have emerged—Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and, most recently, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)—demonstrating that coronaviruses (CoVs) pose a serious threat to human health and highlighting the importance of developing effective therapies against them. Similar to other viruses, CoVs are dependent on host factors for their survival and replication. We hypothesized that evolutionarily distinct CoVs may exploit similar host factors and pathways to support their replication cycles. Herein, we conducted 2 independent genome-wide CRISPR/Cas-9 knockout (KO) screens to identify MERS-CoV and HCoV-229E host dependency factors (HDFs) required for HCoV replication in the human Huh7 cell line. Top scoring genes were further validated and assessed in the context of MERS-CoV and HCoV-229E infection as well as SARS-CoV and SARS-CoV-2 infection. Strikingly, we found that several autophagy-related genes, including TMEM41B, MINAR1, and the immunophilin FKBP8, were common host factors required for pan-CoV replication. Importantly, inhibition of the immunophilin protein family with the compounds cyclosporine A, and the nonimmunosuppressive derivative alisporivir, resulted in dose-dependent inhibition of CoV replication in primary human nasal epithelial cell cultures, which recapitulate the natural site of virus replication. Overall, we identified host factors that are crucial for CoV replication and demonstrated that these factors constitute potential targets for therapeutic intervention by clinically approved drugs.

scholarly journals A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets

2021 ◽  
Author(s):  
Annika Kratzel ◽  
Jenna N. Kelly ◽  
Yannick Brueggemann ◽  
Jasmine Portmann ◽  
Philip V’kovski ◽  
...  
Keyword(s):  
Host Factors ◽  
The Novel ◽  
Genome Wide ◽  
A Genome ◽  
Dependent Inhibition ◽  
Crispr Screen ◽  
Dose Dependent Inhibition ◽  
Autophagy Pathway ◽  
Approved Drugs ◽  
Dose Dependent

SummaryOver the past 20 years, the emergence of three highly pathogenic coronaviruses (CoV) – SARS-CoV, MERS-CoV, and most recently SARS-CoV-2 – has shown that CoVs pose a serious risk to human health and highlighted the importance of developing effective therapies against them. Similar to other viruses, CoVs are dependent on host factors for their survival and replication. We hypothesized that evolutionarily distinct CoVs may exploit similar host factors and pathways to support their replication cycle. Here, we conducted two independent genome-wide CRISPR/Cas9 knockout screens to identify pan-CoV host factors required for the replication of both endemic and emerging CoVs, including the novel CoV SARS-CoV-2. Strikingly, we found that several autophagy-related genes, including the immunophilin FKBP8, TMEM41B, and MINAR1, were common host factors required for CoV replication. Importantly, inhibition of the immunophilin family with the compounds Tacrolimus, Cyclosporin A, and the non-immunosuppressive derivative Alisporivir, resulted in dose-dependent inhibition of CoV replication in primary human nasal epithelial cell cultures that resemble the natural site of virus replication. Overall, we identified host factors that are crucial for CoV replication and demonstrate that these factors constitute potential targets for therapeutic intervention by clinically approved drugs.

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