Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection

Li, Bo; Clohisey, Sara; Chia, Bing Shao; Wang, Bo; Cui, Ang; Eisenhaure, Thomas; Schweitzer, Lawrence D.; Hoover, Paul; Parkinson, Nick; Nachshon, Aharon; Smith, Nikki; Regan, Tim; Farr, David F.; Gutmann, Michael U.; Bukhari, Syed Irfan Ahmad; Law, Andrew; Sangesland, Maya; Gat‐Viks, Irit; Digard, Paul; Vasudevan, Shobha; Lingwood, Daniel; Dockrell, David H.; Doench, John G.; Baillie, J Kenneth; Hacohen, Nir

doi:10.1038/s41467-019-13965-x

Cited by 166 publications

(169 citation statements)

References 86 publications

(113 reference statements)

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“…Genes required for uptake of Ebola, influenza A, and Zika viruses were obtained from published CRISPR screens [31][32][33] . Since the Ebola data were also analysed with MAGeCK, we defined genes required for viral uptake using an unadjusted p-value threshold of 0.01; this information was not available for the influenza A and Zika studies, so we defined genes required for viral uptake as having an adjusted p-value < 0.05.…”

Section: Resultsmentioning

confidence: 99%

Whole genome CRISPR screens identify a LRRK2-regulated pathway for extracellular tau uptake by human neurons

Evans¹,

Strano²,

Campbell³

et al. 2020

Preprint

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Pathological protein aggregation in Alzheimer's disease and other dementias is proposed to spread through the nervous system by a process of intercellular transfer of pathogenic forms of tau protein. Defining the cellular mechanisms of tau entry to human neurons is essential for understanding dementia pathogenesis and the rational design of disease-modifying therapeutics. Using whole genome CRISPR knockout screens in human iPSC-derived excitatory neurons, the primary cell type affected in these diseases, we identified genes and pathways required specifically for uptake of monomeric and aggregated tau. Monomeric and aggregated tau are both taken up by human neurons by receptor-mediated endocytosis, with the low-density lipoprotein LRP1 a significant surface receptor for both forms of tau. Perturbations of the endolysosome and autophagy systems at many levels, and specifically endosome sorting and receptor recycling, greatly reduced tau uptake. Of particular therapeutic interest is that loss of function of the endocytosis and autophagy regulator LRRK2, as well as acute inhibition of its kinase activity, reduced neuronal uptake of monomeric and aggregated tau. Kinase-activating mutations in LRRK2 are a cause of Parkinson's disease accompanied by neuronal tau aggregation, suggesting that LRRK2 mediates tau spreading in vivo and that LRRK2 inhibition has the potential to inhibit interneuronal spread of tau pathology, slowing disease progression. Overall, pathways for tau entry share significant similarity with those required for virus entry by receptor-mediated endocytosis, suggesting that tau spreading is a quasi-infectious process.

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Section: Resultsmentioning

confidence: 99%

Whole genome CRISPR screens identify a LRRK2-regulated pathway for extracellular tau uptake by human neurons

Evans¹,

Strano²,

Campbell³

et al. 2020

Preprint

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“…Since IAV has a relatively small genome, host machinery is required in order to accomplish the viral life cycle. To uncover host dependency factors that are necessary for IAV replication, numerous large-scale RNA interference (RNAi) screens and genome-wide CRISPR/Cas 9 screen were performed [29,[100][101][102][103]. For instance, SON DNA binding protein was important for IAV virion trafficking in an early infection stage and CDC-like kinase 1 facilitated AIV replication [29].…”

Section: Life Cycle Of Influenza a Virusmentioning

confidence: 99%

“…USP47 facilitated viral entry, whereas TNFSF12 (APRIL) and TNFSF12-TNFSF13 (TWEPRIL) helped with viral replication [101]. Using genome-wide CRISPR/Cas9 screen, several genes of sialic acid biosynthesis and related glycosylation pathways were involved with H5N1 infection [102], and WDR7, CCDC115, and TMEM199 were essential for viral entry and regulation of V-type ATPase assembly [103]. Furthermore, single-cell transcriptome sequencing (RNA-seq) was applied to explore host-virus interactions, revealing a correlation between defective viral genomes and virus-induced host transcriptional programs [104].…”

Section: Life Cycle Of Influenza a Virusmentioning

confidence: 99%

Host–Virus Interaction: How Host Cells Defend against Influenza A Virus Infection

Zhang

Cao

2020

Viruses

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Influenza A viruses (IAVs) are highly contagious pathogens infecting human and numerous animals. The viruses cause millions of infection cases and thousands of deaths every year, thus making IAVs a continual threat to global health. Upon IAV infection, host innate immune system is triggered and activated to restrict virus replication and clear pathogens. Subsequently, host adaptive immunity is involved in specific virus clearance. On the other hand, to achieve a successful infection, IAVs also apply multiple strategies to avoid be detected and eliminated by the host immunity. In the current review, we present a general description on recent work regarding different host cells and molecules facilitating antiviral defenses against IAV infection and how IAVs antagonize host immune responses.

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“…Bafilomycin A1, an inhibitor of V-ATPase activity, binds ATP6V0C and inhibits proton translocation into the lysosomal lumen, thus inhibiting lysosomal acidification and cargo degradation (64). Inhibition of endosomal acidification by bafilomycin A1 abolished the infection of several viruses such as dengue virus (65), Zika virus (66), human papillomavirus (67), rhinovirus (68), equine infectious anemia virus (69), murine leukemia virus (70), and influenza A virus (71)(72)(73).…”

Section: Introductionmentioning

confidence: 99%

The viral protein U (Vpu)-interacting host protein ATP6V0C down-regulates cell-surface expression of tetherin and thereby contributes to HIV-1 release

Waheed

Swiderski²,

Khan³

et al. 2020

Journal of Biological Chemistry

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Host proteins with antiviral activity have evolved as first-line defenses to suppress viral replication. The HIV-1 accessory protein viral protein U (Vpu) enhances release of the virus from host cells by down-regulating the cell-surface expression of the host restriction factor tetherin. However, the exact mechanism of Vpu-mediated suppression of antiviral host responses is unclear. To further understand the role of host proteins in Vpu's function, here we carried out yeast two-hybrid screening and identified the V0 subunit C of vacuolar ATPase (ATP6V0C) as a Vpu-binding protein. To examine the role of ATP6V0C in Vpu-mediated tetherin degradation and HIV-1 release, we knocked down ATP6V0C expression in HeLa cells and observed that ATP6V0C depletion impairs Vpu-mediated tetherin degradation, resulting in defective HIV-1 release. We also observed that ATP6V0C overexpression stabilizes tetherin expression. This stabilization effect was specific to ATP6V0C, as overexpression of another subunit of the vacuolar ATPase, ATP6V0C″, had no effect on tetherin expression. ATP6V0C overexpression did not stabilize CD4, another target of Vpu-mediated degradation. Immunofluorescence localization experiments revealed that the ATP6V0C-stabilized tetherin is sequestered in a CD63– and lysosome-associated membrane protein 1 (LAMP1)–positive intracellular compartment. These results indicate that the Vpu-interacting protein ATP6V0C plays a role in down-regulating cell-surface expression of tetherin and thereby contributes to HIV-1 assembly and release.

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Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection

Cited by 166 publications

References 86 publications

Whole genome CRISPR screens identify a LRRK2-regulated pathway for extracellular tau uptake by human neurons

Whole genome CRISPR screens identify a LRRK2-regulated pathway for extracellular tau uptake by human neurons

Host–Virus Interaction: How Host Cells Defend against Influenza A Virus Infection

The viral protein U (Vpu)-interacting host protein ATP6V0C down-regulates cell-surface expression of tetherin and thereby contributes to HIV-1 release

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