Influenza virus exploits tunneling nanotubes for cell-to-cell spread

Kumar, Amrita; Kim, Jin Hyang; Ranjan, Priya; Metcalfe, Maureen G.; Cao, Weiping; Mishina, Margarita; Gangappa, Shivaprakash; Guo, Zhu; Boyden, Edward S.; Zaki, Sherif R.; York, Ian A.; Garcı́a-Sastre, Adolfo; Shaw, Michael; Sambhara, Suryaprakash

doi:10.1038/srep40360

Cited by 122 publications

(165 citation statements)

References 34 publications

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“…In this context, recent evidence show that influenza virus potentially exploits TNT networks for transferring viral proteins and the genome from infected to naïve cells (Kumar et al, 2017). Authors argue that influenza uses these networks for evading immune and antiviral defenses and provide an explanation for the propagation of influenza infections and vaccine failures.…”

Section: Resemblance In Dissemination Of Disease Associated Patternsmentioning

confidence: 99%

Extracellular Vesicles, Tunneling Nanotubes, and Cellular Interplay: Synergies and Missing Links

Nawaz

Fatima

2017

Front. Mol. Biosci.

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The process of intercellular communication seems to have been a highly conserved evolutionary process. Higher eukaryotes use several means of intercellular communication to address both the changing physiological demands of the body and to fight against diseases. In recent years, there has been an increasing interest in understanding how cell-derived nanovesicles, known as extracellular vesicles (EVs), can function as normal paracrine mediators of intercellular communication, but can also elicit disease progression and may be used for innovative therapies. Over the last decade, a large body of evidence has accumulated to show that cells use cytoplasmic extensions comprising open-ended channels called tunneling nanotubes (TNTs) to connect cells at a long distance and facilitate the exchange of cytoplasmic material. TNTs are a different means of communication to classical gap junctions or cell fusions; since they are characterized by long distance bridging that transfers cytoplasmic organelles and intracellular vesicles between cells and represent the process of heteroplasmy. The role of EVs in cell communication is relatively well-understood, but how TNTs fit into this process is just emerging. The aim of this review is to describe the relationship between TNTs and EVs, and to discuss the synergies between these two crucial processes in the context of normal cellular cross-talk, physiological roles, modulation of immune responses, development of diseases, and their combinatory effects in tissue repair. At the present time this review appears to be the first summary of the implications of the overlapping roles of TNTs and EVs. We believe that a better appreciation of these parallel processes will improve our understanding on how these nanoscale conduits can be utilized as novel tools for targeted therapies.

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Section: Resemblance In Dissemination Of Disease Associated Patternsmentioning

confidence: 99%

Extracellular Vesicles, Tunneling Nanotubes, and Cellular Interplay: Synergies and Missing Links

Nawaz

Fatima

2017

Front. Mol. Biosci.

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“…Haley et al demonstrated that astrocytes and oligodendrocytes from human brain tissues were negative for LSTc [81]. Therefore, viruses isolated from PML patients with mutations in VP1 within the sialic acid binding sites could possibly lead to neuroinvasion via a sialic acid-independent manner through interactions with an alternate receptor or through a receptor-independent invasion mechanism that has been demonstrated for other viruses [82, 83]. Further research is necessary to define whether viruses with mutations in VP1 are the infectious form of the virus or whether they arise during CNS invasion and contribute to PML pathogenesis through an alternative mechanism.…”

Section: Pml-associated Vp1 Mutationsmentioning

confidence: 99%

JC Polyomavirus Attachment and Entry: Potential Sites for PML Therapeutics

Mayberry

Nelson

Maginnis

2017

Curr Clin Micro Rpt

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Purpose of review JC polyomavirus (JCPyV) is a significant human pathogen that causes an asymptomatic infection in the kidney in the majority of the population. In immunosuppressed individuals, the virus can become reactivated and spread to the brain, causing the fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). There are currently limited treatment options for this fatal disease. Attachment to receptors and entry into host cells are the initiating events in JCPyV infection and therefore an attractive target for therapeutics to prevent or treat PML. This review provides the current understanding of JCPyV attachment and entry events and the potential therapeutics to target these areas. Recent findings JCPyV attachment and entry to host cells is mediated by α2,6-linked lactoseries tetrasaccharide c (LSTc) and 5-hydroxytryptamine receptors (5-HT2Rs), respectively, and subsequent trafficking to the endoplasmic reticulum is required for infection. Recently, vaccines, monoclonal antibodies, and small molecules have shown promise as anti-viral and PML therapies. Summary This review summarizes our current understanding of JCPyV attachment, entry, and trafficking and the development of potential PML therapeutics that inhibit these critical steps in JCPyV infection.

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“…One difference between the structures concerns cytoskeletal composition. While the initially identified structures were shown to contain actin but not microtubules (Ramírez-Weber and Kornberg, 1999;Rustom et al, 2004;Sowinski et al, 2008;Sartori-Rupp et al, 2019), a number of subsequently identified structures contain microtubules (Önfelt et al, 2006;Gerdes et al, 2013;Osswald et al, 2015;Kumar et al, 2017;Resnik et al, 2018;Kim et al, 2019). Where examined, intermediate filaments have also been identified (Iglič et al, 2007;Ady et al, 2014;Sáenz-de-Santa-María et al, 2017;Resnik et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…A second difference concerns the size of the structures. TNTs are generally defined as having a diameter less than 500 nm (Rustom et al, 2004;Ariazi et al, 2017;Sartori-Rupp et al, 2019), but other structures can be several microns wide (Vidulescu et al, 2004;Osswald et al, 2015;Kumar et al, 2017). These variations have led to use of additional names such as 'microtubes' to reflect the structural differences.…”

Section: Introductionmentioning

confidence: 99%

“…IMTs have been identified in vivo in both Drosophila (Ramírez-Weber and Kornberg, 1999;Roy et al, 2011Roy et al, , 2014Huang et al, 2019) and mammals (Chinnery et al, 2008) suggesting physiological significance. A number of communication functions have been attributed to IMTs, including targeted growth factor transmission (Roy et al, 2011(Roy et al, , 2014, neurotransmitter signaling from epithelial cells (Huang et al, 2019), and direct exchange of cytoplasmic materials including: mitochondria (Kumar et al, 2017;Kretschmer et al, 2019), endosomes/lysosomes (Rustom et al, 2004;Kumar et al, 2017;Sartori-Rupp et al, 2019), plasma membrane proteins (Önfelt and Davis, 2004), mRNA (Haimovich et al, 2017), and microRNAs (Thayanithy et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Tumor microtubes connect pancreatic cancer cells in an Arp2/3 complex-dependent manner

Latario

Schoenfeld

Howarth

et al. 2019

Preprint

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Actin-based tubular connections between cells have been observed in many cell types. Termed "tunneling nanotubes (TNTs)", "membrane nanotubes", "tumor microtubes (TMTs)", or "cytonemes", these protrusions interconnect cells in dynamic networks. Structural features in these protrusions vary between cellular systems, including tubule diameter and presence of microtubules. We find tubular protrusions, which we classify as TMTs, in a pancreatic cancer cell line, DHPC-018. TMTs are present in DHPC-018-derived tumors in mice, as well as in a mouse model of pancreatic cancer and a sub-set of primary human tumors. DHPC-018 TMTs have heterogeneous diameter (0.39 -5.85 m, median 1.92 m) and contain actin filaments, microtubules, and cytokeratin 19-based intermediate filaments. The actin filaments are cortical within the protrusion, as opposed to TNTs, in which filaments run down the center of the tube. TMTs are dynamic in length, but are long-lived (median > 60 min). Inhibition of actin polymerization, but not microtubules, results in TMT loss. A second class of tubular protrusion, which we term cell-substrate protrusion (CSP), has similar width range and cytoskeletal features but make contact with the substratum as opposed to another cell. Similar to previous work on TNTs, we find two assembly mechanisms for TMTs, which we term "pull-away" and "search-andcapture".

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Influenza virus exploits tunneling nanotubes for cell-to-cell spread

Cited by 122 publications

References 34 publications

Extracellular Vesicles, Tunneling Nanotubes, and Cellular Interplay: Synergies and Missing Links

Extracellular Vesicles, Tunneling Nanotubes, and Cellular Interplay: Synergies and Missing Links

JC Polyomavirus Attachment and Entry: Potential Sites for PML Therapeutics

Tumor microtubes connect pancreatic cancer cells in an Arp2/3 complex-dependent manner

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