scholarly journals Virus-Mediated Cell-Cell Fusion

2020 ◽  
Vol 21 (24) ◽  
pp. 9644
Author(s):  
Héloïse Leroy ◽  
Mingyu Han ◽  
Marie Woottum ◽  
Lucie Bracq ◽  
Jérôme Bouchet ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Fusion Proteins ◽  
Target Cells ◽  
Special Focus ◽  
Human Pathogens ◽  
General Process ◽  
Tissue Organization ◽  
Donor Cells ◽  
Infected Cells ◽  
Cell Cell

Cell-cell fusion between eukaryotic cells is a general process involved in many physiological and pathological conditions, including infections by bacteria, parasites, and viruses. As obligate intracellular pathogens, viruses use intracellular machineries and pathways for efficient replication in their host target cells. Interestingly, certain viruses, and, more especially, enveloped viruses belonging to different viral families and including human pathogens, can mediate cell-cell fusion between infected cells and neighboring non-infected cells. Depending of the cellular environment and tissue organization, this virus-mediated cell-cell fusion leads to the merge of membrane and cytoplasm contents and formation of multinucleated cells, also called syncytia, that can express high amount of viral antigens in tissues and organs of infected hosts. This ability of some viruses to trigger cell-cell fusion between infected cells as virus-donor cells and surrounding non-infected target cells is mainly related to virus-encoded fusion proteins, known as viral fusogens displaying high fusogenic properties, and expressed at the cell surface of the virus-donor cells. Virus-induced cell-cell fusion is then mediated by interactions of these viral fusion proteins with surface molecules or receptors involved in virus entry and expressed on neighboring non-infected cells. Thus, the goal of this review is to give an overview of the different animal virus families, with a more special focus on human pathogens, that can trigger cell-cell fusion.

scholarly journals Arabidopsis HAP2/GCS1 is a gamete fusion protein homologous to somatic and viral fusogens

2016 ◽  
Author(s):  
Clari Valansi ◽  
David Moi ◽  
Evgenia Leikina ◽  
Elena Matveev ◽  
Martín Graña ◽  
...  
Keyword(s):  
Sexual Reproduction ◽  
Somatic Cell ◽  
Cell Fusion ◽  
Fusion Proteins ◽  
Mammalian Cells ◽  
Generative Cell ◽  
Target Cells ◽  
Complete Fusion ◽  
Gamete Fusion ◽  
Cell Cell

AbstractCell-cell fusion is inherent to any form of sexual reproduction. Loss of HAPLESS 2/GENERATIVE CELL SPECIFIC 1 (HAP2/GCS1) proteins results in gamete fusion failure in different organisms but their exact role is unclear. Here we show that Arabidopsis HAP2/GCS1 expression in mammalian cells is sufficient to promote cell-cell fusion. Hemifusion and complete fusion depend on HAP2/GCS1 presence in both fusing cells. Furthermore, expression of HAP2 on the surface of pseudotyped vesicular stomatitis virus and on the target cells results in HAP2-dependent virus-cell fusion. This bilateral requirement can be bypassed by replacing the plant gene with C. elegans EFF-1 somatic cell fusogen in one of the fusing cells or the virus, indicating that HAP2/GCS1 and EFF-1 share a similar fusion mechanism. Structural modeling of the HAP2/GCS1 protein family predicts that they are homologous to EFF-1 and class II fusion proteins from enveloped viruses (e.g. dengue and Zika viruses). We name this superfamily FUSEXINS: FUSion proteins essential for sexual reproduction and EXoplasmic merger of plasma membranes. Thus, Fusexins unify the origin and evolution of sexual reproduction, enveloped virus entry into cells and somatic cell fusion.

scholarly journals Fragments of Target Cells are Internalized into Retroviral Envelope Protein-Expressing Cells during Cell-Cell Fusion by Endocytosis

2016 ◽  
Vol 6 ◽  
Author(s):  
Mai Izumida ◽  
Haruka Kamiyama ◽  
Takashi Suematsu ◽  
Eri Honda ◽  
Yosuke Koizumi ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Envelope Protein ◽  
Target Cells ◽  
Cell Cell

scholarly journals The Avian Retrovirus Avian Sarcoma/Leukosis Virus Subtype A Reaches the Lipid Mixing Stage of Fusion at Neutral pH

2003 ◽  
Vol 77 (5) ◽  
pp. 3058-3066 ◽  
Author(s):  
Laurie J. Earp ◽  
Sue E. Delos ◽  
Robert C. Netter ◽  
Paul Bates ◽  
Judith M. White
Keyword(s):  
Cell Fusion ◽  
Receptor Binding ◽  
Low Ph ◽  
Target Cells ◽  
Dependent Manner ◽  
Neutral Ph ◽  
Subtype A ◽  
Avian Sarcoma ◽  
Virus Subtype ◽  
Cell Cell

ABSTRACT We previously showed that the envelope glycoprotein (EnvA) of avian sarcoma/leukosis virus subtype A (ASLV-A) binds to liposomes at neutral pH following incubation with its receptor, Tva, at ≥22°C. We also provided evidence that ASLV-C fuses with cells at neutral pH. These findings suggested that receptor binding at neutral pH and ≥22°C is sufficient to activate Env for fusion. A recent study suggested that two steps are necessary to activate avian retroviral Envs: receptor binding at neutral pH, followed by exposure to low pH (W. Mothes et al., Cell 103:679-689, 2000). Therefore, we evaluated the requirements for intact ASLV-A particles to bind to target bilayers and fuse with cells. We found that ASLV-A particles bind stably to liposomes in a receptor- and temperature-dependent manner at neutral pH. Using ASLV-A particles biosynthetically labeled with pyrene, we found that ASLV-A mixes its lipid envelope with cells within 5 to 10 min at 37°C. Lipid mixing was neither inhibited nor enhanced by incubation at low pH. Lipid mixing of ASLV-A was inhibited by a peptide designed to prevent six-helix bundle formation in EnvA; the same peptide inhibits virus infection and EnvA-mediated cell-cell fusion (at both neutral and low pHs). Bafilomycin and dominant-negative dynamin inhibited lipid mixing of Sindbis virus (which requires low pH for fusion), but not of ASLV-A, with host cells. Finally, we found that, although EnvA-induced cell-cell fusion is enhanced at low pH, a mutant EnvA that is severely compromised in its ability to support infection still induced massive syncytia at low pH. Our results indicate that receptor binding at neutral pH is sufficient to activate EnvA, such that ASLV-A particles bind hydrophobically to and merge their membranes with target cells. Possible roles for low pH at subsequent stages of viral entry are discussed.

Semliki Forest virus induced cell-cell fusion at neutral extracellular pH

1990 ◽  
Vol 10 (4) ◽  
pp. 363-374 ◽  
Author(s):  
Christoph Kempf ◽  
Marcel R. Michel ◽  
Adames Omar ◽  
Pia Jentsch ◽  
Andreas Morell
Keyword(s):  
Cell Fusion ◽  
Semliki Forest Virus ◽  
Covalent Modification ◽  
Surface Proteins ◽  
Acidic Ph ◽  
Fusion Event ◽  
Cell Surface Proteins ◽  
Infected Cells ◽  
Peptide Segments ◽  
Cell Cell

Semliki Forest virus-induced cell-cell fusion from within was considered to exclusively occur at mildly acidic pH (<6.2). Data of this study show that such cell fusion can also be triggered by transient acidification of the cytoplasm of infected cells at an extracellular, neutral pH. Results were obtained by utilizing NH4Cl pulses combined with covalent modification of cell surface proteins. The observation implies a revision of the current consensus regarding the mechanism of Semliki Forest virus induced cell-cell fusion. We propose a model in which at least two peptide segments of the viral spike protein E1 may be involved in triggering the fusion event.

scholarly journals Efficient dissemination of prions through preferential transmission to nearby cells

2007 ◽  
Vol 88 (2) ◽  
pp. 706-713 ◽  
Author(s):  
Sophie Paquet ◽  
Christelle Langevin ◽  
Jérome Chapuis ◽  
Graham S. Jackson ◽  
Hubert Laude ◽  
...  
Keyword(s):  
Experimental Approach ◽  
Critical Issue ◽  
Target Cells ◽  
Cell Analysis ◽  
Infectious Agents ◽  
Donor Cells ◽  
Infected Cells ◽  
Range Spread ◽  
Cell Spread ◽  
Insight Into

Despite circumstantial evidence that prions can be found extracellularly or at the surface of infected cells, little is known about how these infectious agents spread from cell to cell. In order to gain better insight into this critical issue, this study used two different cell lines (neuroglial MovS and epithelial Rov cells) that have previously been shown to be permissive for ovine prion multiplication. Co-culture of infected cells and uninfected target cells at a ratio of 1 : 9 resulted in total infection of MovS cells within 10 days but not of Rov cell cultures, suggesting that the efficiency of prion dissemination may vary greatly depending on the type of permissive cell. Analysis of the spatial distribution of the newly infected cells revealed that, although long-range spread could also occur, cells proximal to the infected donor cells consistently accumulated more abnormal PrP, consistent with preferential infection of nearby cells. This experimental approach, focused on dissemination among living cells, could help in the analysis of mechanisms involved in the cell-to-cell spread of prion infections.

scholarly journals Antigenic Properties of the Human Immunodeficiency Virus Envelope during Cell-Cell Fusion

2001 ◽  
Vol 75 (22) ◽  
pp. 11096-11105 ◽  
Author(s):  
Catherine M. Finnegan ◽  
Werner Berg ◽  
George K. Lewis ◽  
Anthony L. DeVico
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Fusion ◽  
Target Cell ◽  
Binding Domain ◽  
Target Cells ◽  
Coreceptor Binding ◽  
Antigenic Properties ◽  
Immunodeficiency Virus ◽  
Cell Interface ◽  
Cell Cell

ABSTRACT Human immunodeficiency virus (HIV) fusion and entry involves sequential interactions between the viral envelope protein, gp120, cell surface CD4, and a G-protein-coupled coreceptor. Each interaction creates an intermediate gp120 structure predicted to display distinct antigenic features, including key functional domains for viral entry. In this study, we examined the disposition of these features during the fusion of HeLa cells expressing either HIVHXB2 envelope (Env cells) or CXCR4 and CD4 (target cells). Cell-cell fusion, indicated by cytoplasmic dye transfer, was allowed to progress for various times and then arrested. The cells were then examined for reactivity with antibodies directed against receptor-induced epitopes on gp120. Analyses of cells arrested by cooling to 4°C revealed that antibodies against the CD4-induced coreceptor-binding domain, i.e., 17b, 48d, and CG10, faintly react with Env cells even in the absence of target cell or soluble CD4 (sCD4) interactions. Such reactivity increased after exposure to sCD4 but remained unchanged during fusion with target cells and was not intensified at the Env-target cell interface. Notably, the antibodies did not react with Env cells when treated with a covalent cross-linker either alone or during fusion with target cells. Immunoreactivity could not be promoted or otherwise altered on either temperature arrested or cross-linked cells by preventing coreceptor interactions or by using a 17b Fab. In comparison, two other gp120-CD4 complex-dependent antibodies against epitopes outside the coreceptor domain, 8F101 and A32, exhibited a different pattern of reactivity. These antibodies reacted with the Env-target cell interface only after 30 min of cocultivation, concurrent with the first visible transfer of cytoplasmic dye from Env to target cells. At later times, the staining surrounded entire syncytia. Such binding was entirely dependent on the formation of gp120-CD4-CXCR4 tricomplexes since staining was absent with SDF-treated or coreceptor-negative target cells. Overall, these studies show that access to the CD4-induced coreceptor-binding domain on gp120 is largely blocked at the fusing cell interface and is unlikely to represent a target for neutralizing antibodies. However, new epitopes are presented on intermediate gp120 structures formed as a result of coreceptor interactions. Such findings have important implications for HIV vaccine approaches based on conformational alterations in envelope structures.

scholarly journals Antigenic Properties of the Human Immunodeficiency Virus Transmembrane Glycoprotein during Cell-Cell Fusion

2002 ◽  
Vol 76 (23) ◽  
pp. 12123-12134 ◽  
Author(s):  
Catherine M. Finnegan ◽  
Werner Berg ◽  
George K. Lewis ◽  
Anthony L. DeVico
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Fusion ◽  
Target Cells ◽  
Dye Transfer ◽  
Temperature Dependent ◽  
Gp41 Ectodomain ◽  
Immunodeficiency Virus ◽  
Hiv Envelope ◽  
Soluble Cd4 ◽  
Cell Cell

ABSTRACT Human immunodeficiency virus (HIV) entry is triggered by interactions between a pair of heptad repeats in the gp41 ectodomain, which convert a prehairpin gp41 trimer into a fusogenic three-hairpin bundle. Here we examined the disposition and antigenic nature of these structures during the HIV-mediated fusion of HeLa cells expressing either HIVHXB2 envelope (Env cells) or CXCR4 and CD4 (target cells). Cell-cell fusion, indicated by cytoplasmic dye transfer, was allowed to progress for various lengths of time and then arrested. Fusion intermediates were then examined for reactivity with various monoclonal antibodies (MAbs) against immunogenic cluster I and cluster II epitopes in the gp41 ectodomain. All of these MAbs produced similar staining patterns indicative of reactivity with prehairpin gp41 intermediates or related structures. MAb staining was seen on Env cells only upon exposure to soluble CD4, CD4-positive, coreceptor-negative cells, or stromal cell-derived factor-treated target cells. In the fusion system, the MAbs reacted with the interfaces of attached Env and target cells within 10 min of coculture. MAb reactivity colocalized with the formation of gp120-CD4-coreceptor tricomplexes after longer periods of coculture, although reactivity was absent on cells exhibiting cytoplasmic dye transfer. Notably, the MAbs were unable to inhibit fusion even when allowed to react with soluble-CD4-triggered or temperature-arrested antigens prior to initiation of the fusion process. In comparison, a broadly neutralizing antibody, 2F5, which recognizes gp41 antigens in the HIV envelope spike, was immunoreactive with free Env cells and Env-target cell clusters but not with fused cells. Notably, exposure of the 2F5 epitope required temperature-dependent elements of the HIV envelope structure, as MAb binding occurred only above 19°C. Overall, these results demonstrate that immunogenic epitopes, both neutralizing and nonneutralizing, are accessible on gp41 antigens prior to membrane fusion. The 2F5 epitope appears to depend on temperature-dependent elements on prefusion antigens, whereas cluster I and cluster II epitopes are displayed by transient gp41 structures. Such findings have important implications for HIV vaccine approaches based on gp41 intermediates.

scholarly journals Cell surface effects of human immunodeficiency virus

1988 ◽  
Vol 8 (1) ◽  
pp. 35-48 ◽  
Author(s):  
Robert F. Garry ◽  
A. Arthur Gottlieb ◽  
Kenneth P. Zuckerman ◽  
John R. Pace ◽  
Thomas W. Frank ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Surface ◽  
Cell Fusion ◽  
Surface Effects ◽  
Cell Killing ◽  
Viral Envelope ◽  
Rational Approach ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Cell Cell

Cell killing by human immunodeficiency virus (HIV) is thought to contribute to many of the defects of the acquired immunodeficiency syndrome (AIDS). Two types of cytopathology are observed in HIV-infected cultured cells: cell-cell fusion and killing of single cells. Both killing processes appear to involve cell surface effects of HIV. A model is proposed for the HIV-mediated cell surface processes which could result in cell-cell fusion and single cell killing. The purpose of this model is to define the potential roles of individual viral envelope and cell surface molecules in cell killing processes and to identify alternative routes to the establishment of persistently-infected cells. Elucidation of HIV-induced cell surface effects may provide the basis for a rational approach to the design of antiviral agents which are selective for HIV-infected cells.

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