Avoiding the void: cell-to-cell spread of human viruses

Sattentau, Quentin J.

doi:10.1038/nrmicro1972

Cited by 550 publications

(545 citation statements)

References 135 publications

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“…Additionally, virus particles might be retained on the cell surface in a biofi lm-like structure before being laterally transferred to recipient cells that are outside of cell-cell contact regions 27 . Whereas HTLV-1 infects mobile cells (lymphocytes), the virological synapse maximizes transmission effi ciency and limits virus exposure to host defense mechanisms 28 .…”

Section: Cell-to-cell Spread: the Htlv-1 Virological Synapsementioning

confidence: 99%

Sexual transmission of human T-cell lymphotropic virus type 1

Paiva

Casseb

2014

Rev. Soc. Bras. Med. Trop.

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Human T-cell lymphotropic virus type 1 (HTLV-1) is endemic in many parts of the world and is primarily transmitted through sexual intercourse or from mother to child. Sexual transmission occurs more effi ciently from men to women than women to men and might be enhanced by sexually transmitted diseases that cause ulcers and result in mucosal ruptures, such as syphilis, herpes simplex type 2 (HSV-2), and chancroid. Other sexually transmitted diseases might result in the recruitment of infl ammatory cells and could increase the risk of HTLV-1 acquisition and transmission. Additionally, factors that are associated with higher transmission risks include the presence of antibodies against the viral oncoprotein Tax (anti-Tax), a higher proviral load in peripheral blood lymphocytes, and increased cervicovaginal or seminal secretions. Seminal fl uid has been reported to increase HTLV replication and transmission, whereas male circumcision and neutralizing antibodies might have a protective effect. Recently, free virions were discovered in plasma, which reveals a possible new mode of HTLV replication. It is unclear how this discovery might affect the routes of HTLV transmission, particularly sexual transmission, because HTLV transmission rates are signifi cantly higher from men to women than women to men.

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Section: Cell-to-cell Spread: the Htlv-1 Virological Synapsementioning

confidence: 99%

Sexual transmission of human T-cell lymphotropic virus type 1

Paiva

Casseb

2014

Rev. Soc. Bras. Med. Trop.

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“…A s a pathogen with limited genomic coding capacity, HIV subverts many physiological processes of its host to facilitate key aspects of its own replication. Cell-cell interactions (1,2) that play a critical role in normal immune system function are exploited by the virus to facilitate its transmission from antigenpresenting cells such as dendritic cells to susceptible target CD4 + T cells via a specialized structure designated a virological synapse (3,4). Although virological synapses can also be formed between uninfected and infected T cells (5)(6)(7), such synapses appear to be less tightly structured than synapses between dendritic cells and CD4 + T cells.…”

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confidence: 99%

3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells

Felts

Narayan

Estes

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

175

176

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The efficiency of HIV infection is greatly enhanced when the virus is delivered at conjugates between CD4 + T cells and virus-bearing antigen-presenting cells such as macrophages or dendritic cells via specialized structures known as virological synapses. Using ion abrasion SEM, electron tomography, and superresolution light microscopy, we have analyzed the spatial architecture of cell-cell contacts and distribution of HIV virions at virological synapses formed between mature dendritic cells and T cells. We demonstrate the striking envelopment of T cells by sheet-like membrane extensions derived from mature dendritic cells, resulting in a shielded region for formation of virological synapses. Within the synapse, filopodial extensions emanating from CD4 + T cells make contact with HIV virions sequestered deep within a 3D network of surface-accessible compartments in the dendritic cell. Viruses are detected at the membrane surfaces of both dendritic cells and T cells, but virions are not released passively at the synapse; instead, virus transfer requires the engagement of T-cell CD4 receptors. The relative seclusion of T cells from the extracellular milieu, the burial of the site of HIV transfer, and the receptor-dependent initiation of virion transfer by T cells highlight unique aspects of cell-cell HIV transmission.

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“…Viruses exploit and manipulate cell-cell contacts for efficient spreading (12,18,32,37,43). In the case of the human immunodeficiency virus (HIV) and the human T cell lymphoma virus these cell-cell contacts share features with immunological synapses and have been designated infectious or virological synapses (13,14,19,29,41).…”

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confidence: 99%

Viral Determinants of Polarized Assembly for the Murine Leukemia Virus

Jin

Mothes

2011

J Virol

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Retrovirus transmission via direct cell-cell contact is more efficient than diffusion through the extracellular milieu. This is believed to be due to the ability of viruses to efficiently coordinate several steps of the retroviral life cycle at cell-cell contact sites (D. Viruses exploit and manipulate cell-cell contacts for efficient spreading (12,18,32,37,43). In the case of the human immunodeficiency virus (HIV) and the human T cell lymphoma virus these cell-cell contacts share features with immunological synapses and have been designated infectious or virological synapses (13,14,19,29,41). Using the murine leukemia virus (MLV) as a model system, we demonstrated that the interaction between the viral Env glycoprotein (Env), expressed on the infected cell and the viral receptor, expressed on the uninfected target cell, leads to the establishment of cell-cell contacts (32, 45). Importantly, following the establishment of cellcell adhesion, assembly was polarized toward the cell-cell contact (16). These data suggested that the infected cell can "sense" the uninfected cell and direct the viral components needed to assemble viruses toward the uninfected cell. Sensing of the target cell turned out to be mediated by the accumulation of Env and receptor at the cell-cell interface and depending on the presence of a cytoplasmic tail (C-tail) of Env, MLV Gag was recruited toward the site of cell-cell contact. Here, we identify a tyrosine residue within the C-tail of Env and matrix within Gag as the viral determinants responsible for this process.C MATERIALS AND METHODSPlasmids and reagents. Mutant MLV envelope expression vectors were generated by site-directed mutagenesis based on the Friend MLV envelope expression vector previously described (16,46). MLV Gag-GFP expression vector was made by fusing enhanced green fluorescent protein (eGFP) to C-terminal of Gag and deleting a large fragment of Pol in full-length Friend57 MLV expression vector pLRB303 (23,35). Individual domains of MLV Gag-GFP were deleted or replaced by a standard overlapping PCR approach. MLV Gag-YFP expression vector was previously described (46). Chimeric MLV Gag with MA swapped with HIV MA was kindly provided by Marc Johnson, University of Missouri. HIV Gag-GFP expression vector and chimeric HIV Gag with MA swapped with MLV MA were described previously (17). HEK293 and XC cells were previously described (16).Visualizing virus cell-to-cell transmission. HEK293 cells were transfected with indicated plasmids by FuGENE 6 and cocultured 4 h posttransfection with XC cells expressing mCherry or cyan fluorescent protein (CFP)-tagged mCAT-1 as previously described (16). The formation of MLV synapses was reproducibly observed 2 to 6 postinitiation of cocultures for MLV generated by the tripartite system (MLV GagPol, Gag-YFP, MLV LTR, and MLV Env) or 4 to 10 h postinitiation of cocultures for MLV generated using proviral pLRB303-derived constructs. Imaging of fixed samples, as well as live-cell imaging, was performed using spinning disc confocal microscopy as ...

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Avoiding the void: cell-to-cell spread of human viruses

Cited by 550 publications

References 135 publications

Sexual transmission of human T-cell lymphotropic virus type 1

Sexual transmission of human T-cell lymphotropic virus type 1

3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells

Viral Determinants of Polarized Assembly for the Murine Leukemia Virus

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