An Evolutionarily Conserved Pathway Essential for Orsay Virus Infection of
            <i>Caenorhabditis elegans</i>

Jiang, Hongbing; Chen, Kevin; Sandoval, Luis; Leung, Christian; Wang, David

doi:10.1128/mbio.00940-17

Cited by 49 publications

(87 citation statements)

References 51 publications

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“…Additional culture models are needed to handle all the new discoveries and genetic engineering methods for more easily establishing cell lines from exotic species are worth pursuing (Ettayebi et al, 2016;Finkbeiner et al, 2012;Stenglein et al, 2012;Bell-Sakyi and Attoui, 2016;Janowski et al, 2017). Focusing discovery on genetically tractable organisms has allowed for relatively rapid functional studies of the new discovered C. elegans Orsay virus Jiang et al, 2017). A number of culture-independent methods exist now to characterize the novel viruses and their genes.…”

Section: Experimenting With Functionmentioning

confidence: 99%

A decade of RNA virus metagenomics is (not) enough

2018

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It is hard to overemphasize the role that metagenomics has had on our recent understanding of RNA virus diversity. Metagenomics in the 21st century has brought with it an explosion in the number of RNA virus species, genera, and families far exceeding that following the discovery of the microscope in the 18th century for eukaryotic life or culture media in the 19th century for bacteriology or the 20th century for virology. When the definition of success in organism discovery is measured by sequence diversity and evolutionary distance, RNA viruses win. This review explores the history of RNA virus metagenomics, reasons for the successes so far in RNA virus metagenomics, and methodological concerns. In addition, the review briefly covers clinical metagenomics and environmental metagenomics and highlights some of the critical accomplishments that have defined the fast pace of RNA virus discoveries in recent years. Slightly more than a decade in, the field is exhausted from its discoveries but knows that there is yet even more out there to be found.

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Section: Experimenting With Functionmentioning

confidence: 99%

A decade of RNA virus metagenomics is (not) enough

2018

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“…We previously determined that the C. elegans genes sid-3, viro-2 , and nck-1 are essential for Orsay virus infection in C. elegans (10). In this study, we further asked whether their respective human orthologues TNK2, WASL, and NCK1 play any roles in mammalian virus infection.…”

Section: Discussionmentioning

confidence: 99%

“…Our study of TNK2 was driven by our identification in C. elegans of sid-3 as a host factor required for Orsay virus infection (10). sid-3 was originally identified in a genetic screen for mutants defective in systemic spread of RNAi (51).…”

Section: Discussionmentioning

confidence: 99%

“…In C. elegans , Orsay virus infection is presumed to occur by fecal-oral transmission, as evidenced by its exclusive intestinal cell tropism (57). Deletion of sid-3 reduces Orsay virus infection by > 5 logs in vivo in the C. elegans host (10). In the current study, infection of mice lacking TNK2 by oral gavage, the analogous route of infection as for Orsay virus infection of C elegans , led to increased survival of animals deficient in TNK2.…”

Section: Discussionmentioning

confidence: 99%

“…Using a novel virus infection system comprised of the model organism C. elegans and Orsay virus, the only known natural virus of C. elegans , we previously identified several genes that are essential for virus infection in C. elegans (10). The genes sid-3, viro-2 and nck-1 were found to be essential for an early, pre-replication step of the Orsay virus lifecycle.…”

Section: Introductionmentioning

confidence: 99%

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Entry by multiple picornaviruses is dependent on a pathway that includes TNK2, WASL and NCK1

Jiang

Leung

Tahan

et al. 2019

Preprint

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21 Comprehensive knowledge of the host factors required for picornavirus infection would 22 facilitate antiviral development. Here we demonstrate roles for three human genes, TNK2, WASL, and 23 NCK1, in infection by multiple picornaviruses. CRISPR deletion of TNK2, WASL or NCK1 reduced 24 encephalomyocarditis virus (EMCV), coxsackievirus B3 (CVB3), poliovirus and enterovirus D68 infection, 25 and chemical inhibitors of TNK2 and WASL decreased EMCV infection. Reduced EMCV lethality was 26 observed in mice lacking TNK2. TNK2, WASL and NCK1 were important in early stages of the viral 27 lifecycle, and genetic epistasis analysis demonstrated that the three genes function in a common 28 pathway. Mechanistically, reduced internalization of EMCV was observed in TNK2 deficient cells 29 demonstrating that TNK2 functions in EMCV entry. Domain analysis of WASL demonstrated that its 30 actin nucleation activity was necessary to facilitate viral infection. Together, these data support a model 31 wherein TNK2, WASL, and NCK1 comprise a pathway critical for multiple picornaviruses. 32 33 Introduction 34 Picornaviruses cause a wide range of diseases including the common cold, hepatitis, myocarditis, 35 poliomyelitis, meningitis, and encephalitis (1). Although vaccines exist for poliovirus and hepatitis A virus, 36there are currently no FDA approved antivirals against picornaviruses in the United States. As obligate 37 intracellular pathogens, viruses are dependent on the host cellular machinery to complete their lifecycle. 38Targeting of such host cellular factors in the design of antiviral drugs can circumvent resistance that 39 arises from rapid mutation of viruses. The early stages of the virus lifecycle, including receptor binding, 40 entry, uncoating, and initiation of replication, are the ideal targets for preventing virus infection since 41 the virus has not yet multiplied. 42Despite extensive studies (2), there remain significant gaps in our understanding of virus entry. 43As the family Picornaviridae encompasses a wide range of viruses, it is not surprising that there is 44 diversity in the known entry mechanisms of different species. Among the picornaviruses, poliovirus 45 entry has been the most extensively studied. While some reports suggest that poliovirus enters the cell 46 through clathrin-mediated endocytosis and that its genome release depends on endosome acidification 47(3), more recent studies report that poliovirus enters cells by a clathrin-, caveolin-, flotillin-, and 48 microtubule-independent pathway (4). Furthermore, poliovirus entry is sensitive to inhibitors of both 49 tyrosine kinases and actin-polymerization, although it is not known which specific tyrosine kinase(s) 50 is/are critical for poliovirus infection (4). Coxsackie virus B3 (CVB3) entry has also been extensively 51 studied (5). In polarized epithelial cells, CVB3 binding to the co-receptor decay-accelerating factor (DAF) 52 and the coxsackievirus and adenovirus receptor (CAR) leads to entry by caveolin-dependent endocytosis 53 and macropino...

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Similarities in the induction of the intracellular pathogen response in Caenorhabditis elegans and the type I interferon response in mammals

Lažetić,

Batachari,

Russell

et al. 2023

BioEssays

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Although the type‐I interferon (IFN‐I) response is considered vertebrate‐specific, recent findings about the Intracellular Pathogen Response (IPR) in nematode Caenorhabditis elegans indicate that there are similarities between these two transcriptional immunological programs. The IPR is induced during infection with natural intracellular fungal and viral pathogens of the intestine and promotes resistance against these pathogens. Similarly, the IFN‐I response is induced by viruses and other intracellular pathogens and promotes resistance against infection. Whether the IPR and the IFN‐I response evolved in a divergent or convergent manner is an unanswered and exciting question, which could be addressed by further studies of immunity against intracellular pathogens in C. elegans and other simple host organisms. Here we highlight similar roles played by RIG‐I‐like receptors, purine metabolism enzymes, proteotoxic stressors, and transcription factors to induce the IPR and IFN‐I response, as well as the similar consequences of these defense programs on organismal development.

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An Evolutionarily Conserved Pathway Essential for Orsay Virus Infection of Caenorhabditis elegans

Cited by 49 publications

References 51 publications

A decade of RNA virus metagenomics is (not) enough

A decade of RNA virus metagenomics is (not) enough

Entry by multiple picornaviruses is dependent on a pathway that includes TNK2, WASL and NCK1

Similarities in the induction of the intracellular pathogen response in Caenorhabditis elegans and the type I interferon response in mammals

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