Viral synapse

Viral synapse (or virological synapse) is a molecularly organized cellular junction that is similar in some aspects to immunological synapses.[1] Many viruses including herpes simplex virus (HSV), human immunodeficiency virus (HIV) and human T-lymphotropic virus (HTLV) have been shown to instigate the formation of these junctions between the infected ("donor") and uninfected ("target") cell to allow cell-to-cell transmission.[2][3][4] As viral synapses allow the virus to spread directly from cell to cell, they also provide a means by which the virus can escape neutralising antibody.

Formation and function

Formation of these synapses has been shown to involve reorientation of the cytoskeleton, which is triggered by engagement of ICAM-1 on the infected cell's surface and expression of several viral proteins. Viruses use the microtubule cytoskeleton to migrate to the viral synapse. By recruiting the receptors and viral particles at the point of contact, these synaptic structures significantly enhance the likelihood of a productive infection. Viral synapses are thought to explain how cell-to-cell transfer can operate in the HIV infection even when there is a low number of viral particles and a relatively low number of CD4 receptors.[5][6] Recent study proposes that the primary “killing units” of CD4 T cells leading to CD4 T-cell depletion and progression to AIDS are infected cells (not cell-free viral particles) residing in lymphoid tissues that mediate cell-to-cell spread of the virus via virological synapses.[7] These findings highlight a previously unappreciated role for the virological synapse in HIV pathogenesis.

References
  1. Igakura, T., J. C. Stinchcombe, P. K. C. Goon, G. P. Taylor, J. N. Weber, G. M. Griffiths, Y. Tanaka, M. Osame, and C. R. M. Bangham (2003). "Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton". Science. 299 (5613): 1713–1716. Bibcode:2003Sci...299.1713I. doi:10.1126/science.1080115. PMID 12589003.CS1 maint: multiple names: authors list (link)
  2. Vasiliver-Shamis G, Tuen M, Wu TW, Starr T, Cameron TO, Thomson R, Kaur G, Liu J, Visciano ML, Li H, Kumar R, Ansari R, Han DP, Cho MW, Dustin ML, Hioe CE (2008). "Human immunodeficiency virus type 1 envelope gp120 induces a stop signal and virological synapse formation in noninfected CD4+ T cells". J. Virol. 82 (19): 9445–57. doi:10.1128/JVI.00835-08. PMC 2546991. PMID 18632854.CS1 maint: multiple names: authors list (link)
  3. "Formation of a virological synapse". Retrieved 14 February 2015.
  4. Fernando Abaitua, F. Rabiya Zia, Michael Hollinshead and Peter O'Hare (2013). "Polarized Cell Migration during Cell-to-Cell Transmission of Herpes Simplex Virus in Human Skin Keratinocytes". J. Virol. 87 (14): 7921–7932. doi:10.1128/JVI.01172-13. PMC 3700176. PMID 23658449.CS1 maint: multiple names: authors list (link)
  5. Barnard, A. L., T. Igakura, Y. Tanaka, G. P. Taylor, and C. R. Bangham. (2005). "Engagement of specific T-cell surface molecules regulates cytoskeletal polarization in HTLV-1-infected lymphocytes". Blood. 106 (3): 988–95. doi:10.1182/blood-2004-07-2850. PMID 15831709.CS1 maint: multiple names: authors list (link)
  6. Nejmeddine, M., A. L. Barnard, Y. Tanaka, G. P. Taylor, and C. R. Bangham (2005). "Human T-lymphotropic virus, type 1, tax protein triggers microtubule reorientation in the virological synapse". J. Biol. Chem. 280 (33): 29653–60. doi:10.1074/jbc.M502639200. PMID 15975923.CS1 maint: multiple names: authors list (link)
  7. Galloway NL, Doitsh G, Monroe KM, Yang Z, Muñoz-Arias I, Levy DN, Greene WC (2015). "Cell-to-Cell Transmission of HIV-1 Is Required to Trigger Pyroptotic Death of Lymphoid-Tissue-Derived CD4 T Cells". Cell Rep. 12 (10): 1555–63. doi:10.1016/j.celrep.2015.08.011. PMC 4565731. PMID 26321639.CS1 maint: multiple names: authors list (link)
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