Isolation and Characterization of Pathogen-Bearing Endosomes Enable Analysis of Endosomal Escape and Identification of New Cellular Cofactors of Infection

Scheffer, Konstanze D.; Popa-Wagner, Ruth; Florin, Luise

doi:10.1007/978-1-62703-601-6_7

Cited by 9 publications

(11 citation statements)

References 11 publications

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“…Thus, further work is now required to unravel the contribution of individual tetraspanins in the dynamics of virus-receptor interactions outside and within HPEP. Quantitative proteomics of virus/receptor-complexes on the plasma membrane or in virus-containing endosomes (as described in [105]) will uncover precise molecular composition and stoichiometry of these membrane platforms. In addition, advanced imaging approaches such as super resolution or correlation microscopy will be helpful to examine viral dynamics on the cell surface in more detail.…”

Section: Discussionmentioning

confidence: 99%

The Tetraspanin CD151 in Papillomavirus Infection

Scheffer

Berditchevski

Florin

2014

Viruses

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Human papillomaviruses (HPV) are non-enveloped DNA tumor viruses that infect skin and mucosa. The most oncogenic subtype, HPV16, causes various types of cancer, including cervical, anal, and head and neck cancers. During the multistep process of infection, numerous host proteins are required for the delivery of virus genetic information into the nucleus of target cells. Over the last two decades, many host-cell proteins such as heparan sulfate proteoglycans, integrins, growth factor receptors, actin and the tetraspanin CD151 have been described to be involved in the process of infectious entry of HPV16. Tetraspanins have the ability to organize membrane microdomains and to directly influence the function of associated molecules, including binding of receptors to their ligands, receptor oligomerization and signal transduction. Here, we summarize the current knowledge on CD151, and CD151-associated partners during HPV infection and discuss the underlying mechanisms.

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Section: Discussionmentioning

confidence: 99%

The Tetraspanin CD151 in Papillomavirus Infection

Scheffer

Berditchevski

Florin

2014

Viruses

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“…The protocol for the isolation of endosomes was adapted from Scheffer et al . 59 , Wittrup et al . 60 , Chen et al .…”

Section: Methodsmentioning

confidence: 99%

Short single-stranded DNA degradation products augment the activation of Toll-like receptor 9

et al. 2017

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Toll-like receptors encounter a diversity of degradation products in endosomes. TLR7 and TLR8 have been shown to be activated by RNA degradation products. Here we show that although TLR9 requires single-stranded DNA longer than 20 nucleotides for a robust response, TLR9 activation is augmented by CpG-containing oligodeoxyribonucleotides (sODNs) as short as 2 nucleotides, which, by themselves, do not induce activation in cell cultures, as well as in mice. sODNs also activate human TLR9 in combination with ODNs containing a single CpG motif that by themselves do not activate human TLR9. The specific sequence motif of sODN and colocalization of ODN and sODN suggest that the mechanism of activation involves binding of both ODN and sODN to TLR9. sODNs augment TLR9 activation by mammalian genomic DNA indicating the role of short DNA degradation products in the endosomes in response to infection or in autoimmune disease, particularly at limiting concentrations of ODNs.

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“…The mechanisms apparently vary as in the case of HCV, it is questionable whether association of CD81 with TEMs is truly essential for the early steps of HCV entry (51,54), whereas for other pathogens, such as Plasmodium, association with TEMs is a prerequisite (55). As demonstrated for HPV, virus/TEM association mediates endocytosis during which tetraspanins and viral particles are cointernalized into endosomes (52,56). Our study shows that HPV pseudovirions trigger endocytosis of CD81 molecules organized into platforms and that the formation of functional platforms requires the d-domain.…”

Section: Role Of Cd81 Tems In Pathogen Entry and Targeting Strategiesmentioning

confidence: 99%

The Extracellular δ-Domain is Essential for the Formation of CD81 Tetraspanin Webs

Homsi

Schloetel

Scheffer

et al. 2014

Biophysical Journal

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CD81 is a ubiquitously expressed member of the tetraspanin family. It forms large molecular platforms, so-called tetraspanin webs that play physiological roles in a variety of cellular functions and are involved in viral and parasite infections. We have investigated which part of the CD81 molecule is required for the formation of domains in the cell membranes of T-cells and hepatocytes. Surprisingly, we find that large CD81 platforms assemble via the short extracellular δ-domain, independent from a strong primary partner binding and from weak interactions mediated by palmitoylation. The δ-domain is also essential for the platforms to function during viral entry. We propose that, instead of stable binary interactions, CD81 interactions via the small δ-domain, possibly involving a dimerization step, play the key role in organizing CD81 into large tetraspanin webs and controlling its function.

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Isolation and Characterization of Pathogen-Bearing Endosomes Enable Analysis of Endosomal Escape and Identification of New Cellular Cofactors of Infection

Cited by 9 publications

References 11 publications

The Tetraspanin CD151 in Papillomavirus Infection

The Tetraspanin CD151 in Papillomavirus Infection

Short single-stranded DNA degradation products augment the activation of Toll-like receptor 9

The Extracellular δ-Domain is Essential for the Formation of CD81 Tetraspanin Webs

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