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Viruses
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Viruses and Tetraspanins
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Viruses and Tetraspanins

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 December 2013) | Viewed by 76955

Special Issue Editor

Dr. Markus Thali

E-Mail Website
Guest Editor
Microbiology and Molecular Genetics Department, University of Vermont, Stafford Hall, Room 320, Burlington, VT 05405, USA
Interests: HIV/retrovirus transmission and spread; virus-induced cell-cell fusion; syncytia; virus-host interactions; various quantitative imaging methods; viruses as overall positive biological entities
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tetraspanins control membrane-based processes such as cell-cell adhesion, migration, and fusion of cellular membranes. Not all that surprisingly, then, members of this family of integral membrane proteins have been implicated in the replication of various viruses. These include, among others, retroviruses (e.g. HIV-1 and HTLV), or HCV, the etiological agent for hepatitis C, for which the tetraspanin CD81 (together with other cell-surface molecules) has been shown to be critical for viral entry.

For this special issue of Viruses, we seek reports on research that will elucidate how exactly specific tetraspanins control discrete steps of viral life cycles. It is our hope that, together, these articles will further our understanding of how these molecular scaffolds regulate the interplay between viruses and their hosts.

Prof. Dr. Markus Thali
Guest Editor

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Published Papers (7 papers)

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Research

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2604 KiB  
Article
A Role for CD81 and Hepatitis C Virus in Hepatoma Mobility
by Claire L. Brimacombe, Garrick K. Wilson, Stefan G. Hübscher, Jane A. McKeating and Michelle J. Farquhar
Viruses 2014, 6(3), 1454-1472; https://doi.org/10.3390/v6031454 - 24 Mar 2014
Cited by 9 | Viewed by 7567
Abstract
Tetraspanins are a family of small proteins that interact with themselves, host transmembrane and cytosolic proteins to form tetraspanin enriched microdomains (TEMs) that regulate important cellular functions. Several tetraspanin family members are linked to tumorigenesis. Hepatocellular carcinoma (HCC) is an increasing global health [...] Read more.
Tetraspanins are a family of small proteins that interact with themselves, host transmembrane and cytosolic proteins to form tetraspanin enriched microdomains (TEMs) that regulate important cellular functions. Several tetraspanin family members are linked to tumorigenesis. Hepatocellular carcinoma (HCC) is an increasing global health burden, in part due to the increasing prevalence of hepatitis C virus (HCV) associated HCC. The tetraspanin CD81 is an essential receptor for HCV, however, its role in hepatoma biology is uncertain. We demonstrate that antibody engagement of CD81 promotes hepatoma spread, which is limited by HCV infection, in an actin-dependent manner and identify an essential role for the C-terminal interaction with Ezrin-Radixin-Moesin (ERM) proteins in this process. We show enhanced hepatoma migration and invasion following expression of CD81 and a reduction in invasive potential upon CD81 silencing. In addition, we reveal poorly differentiated HCC express significantly higher levels of CD81 compared to adjacent non-tumor tissue. In summary, these data support a role for CD81 in regulating hepatoma mobility and propose CD81 as a tumour promoter. Full article
(This article belongs to the Special Issue Viruses and Tetraspanins)
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1415 KiB  
Communication
Evidence Showing that Tetraspanins Inhibit HIV-1-Induced Cell-Cell Fusion at a Post-Hemifusion Stage
by Menelaos Symeonides, Marie Lambelé, Nathan H. Roy and Markus Thali
Viruses 2014, 6(3), 1078-1090; https://doi.org/10.3390/v6031078 - 7 Mar 2014
Cited by 25 | Viewed by 8468
Abstract
Human immunodeficiency virus type 1 (HIV-1) transmission takes place primarily through cell-cell contacts known as virological synapses. Formation of these transient adhesions between infected and uninfected cells can lead to transmission of viral particles followed by separation of the cells. Alternatively, the cells [...] Read more.
Human immunodeficiency virus type 1 (HIV-1) transmission takes place primarily through cell-cell contacts known as virological synapses. Formation of these transient adhesions between infected and uninfected cells can lead to transmission of viral particles followed by separation of the cells. Alternatively, the cells can fuse, thus forming a syncytium. Tetraspanins, small scaffolding proteins that are enriched in HIV-1 virions and actively recruited to viral assembly sites, have been found to negatively regulate HIV-1 Env-induced cell-cell fusion. How these transmembrane proteins inhibit membrane fusion, however, is currently not known. As a first step towards elucidating the mechanism of fusion repression by tetraspanins, e.g., CD9 and CD63, we sought to identify the stage of the fusion process during which they operate. Using a chemical epistasis approach, four fusion inhibitors were employed in tandem with CD9 overexpression. Cells overexpressing CD9 were found to be sensitized to inhibitors targeting the pre-hairpin and hemifusion intermediates, while they were desensitized to an inhibitor of the pore expansion stage. Together with the results of a microscopy-based dye transfer assay, which revealed CD9- and CD63-induced hemifusion arrest, our investigations strongly suggest that tetraspanins block HIV-1-induced cell-cell fusion at the transition from hemifusion to pore opening. Full article
(This article belongs to the Special Issue Viruses and Tetraspanins)
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Review

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870 KiB  
Review
Viruses and Tetraspanins: Lessons from Single Molecule Approaches
by Selma Dahmane, Eric Rubinstein and Pierre-Emmanuel Milhiet
Viruses 2014, 6(5), 1992-2011; https://doi.org/10.3390/v6051992 - 5 May 2014
Cited by 14 | Viewed by 8209
Abstract
Tetraspanins are four-span membrane proteins that are widely distributed in multi-cellular organisms and involved in several infectious diseases. They have the unique property to form a network of protein-protein interaction within the plasma membrane, due to the lateral associations with one another and [...] Read more.
Tetraspanins are four-span membrane proteins that are widely distributed in multi-cellular organisms and involved in several infectious diseases. They have the unique property to form a network of protein-protein interaction within the plasma membrane, due to the lateral associations with one another and with other membrane proteins. Tracking tetraspanins at the single molecule level using fluorescence microscopy has revealed the membrane behavior of the tetraspanins CD9 and CD81 in epithelial cell lines, providing a first dynamic view of this network. Single molecule tracking highlighted that these 2 proteins can freely diffuse within the plasma membrane but can also be trapped, permanently or transiently, in tetraspanin-enriched areas. More recently, a similar strategy has been used to investigate tetraspanin membrane behavior in the context of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infection. In this review we summarize the main results emphasizing the relationship in terms of membrane partitioning between tetraspanins, some of their partners such as Claudin-1 and EWI-2, and viral proteins during infection. These results will be analyzed in the context of other membrane microdomains, stressing the difference between raft and tetraspanin-enriched microdomains, but also in comparison with virus diffusion at the cell surface. New advanced single molecule techniques that could help to further explore tetraspanin assemblies will be also discussed. Full article
(This article belongs to the Special Issue Viruses and Tetraspanins)
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688 KiB  
Review
Super-Resolution Microscopy: A Virus’ Eye View of the Cell
by Joe Grove
Viruses 2014, 6(3), 1365-1378; https://doi.org/10.3390/v6031365 - 19 Mar 2014
Cited by 29 | Viewed by 10780
Abstract
It is difficult to observe the molecular choreography between viruses and host cell components, as they exist on a spatial scale beyond the reach of conventional microscopy. However, novel super-resolution microscopy techniques have cast aside technical limitations to reveal a nanoscale view of [...] Read more.
It is difficult to observe the molecular choreography between viruses and host cell components, as they exist on a spatial scale beyond the reach of conventional microscopy. However, novel super-resolution microscopy techniques have cast aside technical limitations to reveal a nanoscale view of virus replication and cell biology. This article provides an introduction to super-resolution imaging; in particular, localisation microscopy, and explores the application of such technologies to the study of viruses and tetraspanins, the topic of this special issue. Full article
(This article belongs to the Special Issue Viruses and Tetraspanins)
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718 KiB  
Review
The Tetraspanin CD151 in Papillomavirus Infection
by Konstanze D. Scheffer, Fedor Berditchevski and Luise Florin
Viruses 2014, 6(2), 893-908; https://doi.org/10.3390/v6020893 - 18 Feb 2014
Cited by 40 | Viewed by 11266
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Viruses and Tetraspanins)
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705 KiB  
Review
CD81-Receptor Associations — Impact for Hepatitis C Virus Entry and Antiviral Therapies
by Laetitia Zona, Rajiv G. Tawar, Mirjam B. Zeisel, Fei Xiao, Catherine Schuster, Joachim Lupberger and Thomas F. Baumert
Viruses 2014, 6(2), 875-892; https://doi.org/10.3390/v6020875 - 18 Feb 2014
Cited by 30 | Viewed by 11613
Abstract
Tetraspanins are integral transmembrane proteins organized in microdomains displaying specific and direct interactions with other tetraspanins and molecular partners. Among them, CD81 has been implicated in a variety of physiological and pathological processes. CD81 also plays a crucial role in pathogen entry into [...] Read more.
Tetraspanins are integral transmembrane proteins organized in microdomains displaying specific and direct interactions with other tetraspanins and molecular partners. Among them, CD81 has been implicated in a variety of physiological and pathological processes. CD81 also plays a crucial role in pathogen entry into host cells, including hepatitis C virus (HCV) entry into hepatocytes. HCV is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV entry into hepatocytes is a complex process that requires the coordinated interaction of viral and host factors for the initiation of infection, including CD81, scavenger receptor BI, claudin-1, occludin, membrane-bound host cell kinases, Niemann-Pick C1 Like 1, Harvey rat sarcoma viral oncogene homolog (HRas), CD63 and transferrin receptor 1. Furthermore, recent data in HCV model systems have demonstrated that targeting critical components of tetraspanins and associated cell membrane proteins open new avenues to prevent and treat viral infection. Full article
(This article belongs to the Special Issue Viruses and Tetraspanins)
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2782 KiB  
Review
CD81 and Hepatitis C Virus (HCV) Infection
by Lucie Fénéant, Shoshana Levy and Laurence Cocquerel
Viruses 2014, 6(2), 535-572; https://doi.org/10.3390/v6020535 - 6 Feb 2014
Cited by 80 | Viewed by 18326
Abstract
Hepatitis C Virus (HCV) infection is a global public health problem affecting over 160 million individuals worldwide. Its symptoms include chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV is an enveloped RNA virus mainly targeting liver cells and for which the initiation of [...] Read more.
Hepatitis C Virus (HCV) infection is a global public health problem affecting over 160 million individuals worldwide. Its symptoms include chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. HCV is an enveloped RNA virus mainly targeting liver cells and for which the initiation of infection occurs through a complex multistep process involving a series of specific cellular entry factors. This process is likely mediated through the formation of a tightly orchestrated complex of HCV entry factors at the plasma membrane. Among HCV entry factors, the tetraspanin CD81 is one of the best characterized and it is undoubtedly a key player in the HCV lifecycle. In this review, we detail the current knowledge on the involvement of CD81 in the HCV lifecycle, as well as in the immune response to HCV infection. Full article
(This article belongs to the Special Issue Viruses and Tetraspanins)
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