Editing HIV (section)

===Spread within the body===
[[File:Virus infecting lymphocytes.gif|left|thumb|Animation demonstrating cell-free spread of HIV]]
The classical process of infection of a cell by a virion can be called "cell-free spread" to distinguish it from a more recently recognized process called "cell-to-cell spread".<ref name=Zhang>{{cite journal | vauthors = Zhang C, Zhou S, Groppelli E, Pellegrino P, Williams I, Borrow P, Chain BM, Jolly C | title = Hybrid Spreading Mechanisms and T Cell Activation Shape the Dynamics of HIV-1 Infection | journal = PLOS Computational Biology | volume = 11 | issue = 4 | pages = e1004179 | year = 2015 | pmid = 25837979 | pmc = 4383537 | doi = 10.1371/journal.pcbi.1004179 | arxiv = 1503.08992 | bibcode = 2015PLSCB..11E4179Z | doi-access = free }}</ref> In cell-free spread (see figure), virus particles bud from an infected T cell, enter the blood or [[extracellular fluid]] and then infect another T cell following a chance encounter.<ref name="Zhang" /> HIV can also disseminate by direct transmission from one cell to another by a process of cell-to-cell spread, for which two pathways have been described. Firstly, an infected T cell can transmit virus directly to a target T cell via a [[Viral synapse|virological synapse]].<ref name="Arthos" /><ref name=Jolly>{{cite journal | vauthors = Jolly C, Kashefi K, Hollinshead M, Sattentau QJ | title = HIV-1 cell to cell transfer across an Env-induced, actin-dependent synapse | journal = Journal of Experimental Medicine | volume = 199 | issue = 2 | pages = 283–293 | year = 2004| pmid = 14734528 | pmc = 2211771 | doi = 10.1084/jem.20030648 }}</ref> Secondly, an [[antigen-presenting cell]] (APC), such as a macrophage or dendritic cell, can transmit HIV to T cells by a process that either involves productive infection (in the case of macrophages) or capture and transfer of virions ''in trans'' (in the case of dendritic cells).<ref name=Sattentau>{{cite journal | vauthors = Sattentau Q | title = Avoiding the void: cell-to-cell spread of human viruses | journal = Nature Reviews Microbiology | volume = 6 | issue = 11 | pages = 815–826 | year = 2008| pmid = 18923409 | doi = 10.1038/nrmicro1972 | s2cid = 20991705 | doi-access = free }}</ref> Whichever pathway is used, infection by cell-to-cell transfer is reported to be much more efficient than cell-free virus spread.<ref name=Duncan>{{cite journal | vauthors = Duncan CJ, Russell RA, Sattentau QJ | title = High multiplicity HIV-1 cell-to-cell transmission from macrophages to CD4+ T cells limits antiretroviral efficacy | journal = AIDS | volume = 27 | issue = 14 | pages = 2201–2206 | year = 2013 | pmid = 24005480 | pmc = 4714465 | doi = 10.1097/QAD.0b013e3283632ec4 }}</ref> A number of factors contribute to this increased efficiency, including polarised virus budding towards the site of cell-to-cell contact, close apposition of cells, which minimizes fluid-phase [[diffusion]] of virions, and clustering of HIV entry receptors on the target cell towards the contact zone.<ref name="Jolly" /> Cell-to-cell spread is thought to be particularly important in [[lymphoid tissue]]s, where CD4<sup>+</sup> T cells are densely packed and likely to interact frequently.<ref name="Zhang" /> [[Intravital microscopy|Intravital imaging]] studies have supported the concept of the HIV virological synapse ''in vivo''.<ref name=Sewald>{{cite journal | vauthors = Sewald X, Gonzalez DG, Haberman AM, Mothes W | title = In vivo imaging of virological synapses | journal = Nature Communications | volume = 3 | pages =  1320 | year = 2012 | pmid = 23271654 | pmc = 3784984 | doi = 10.1038/ncomms2338 | bibcode = 2012NatCo...3.1320S }}</ref> The many dissemination mechanisms available to HIV contribute to the virus' ongoing replication in spite of anti-retroviral therapies.<ref name="Zhang" /><ref name=Sigal>{{cite journal | vauthors = Sigal A, Kim JT, Balazs AB, Dekel E, Mayo A, Milo R, Baltimore D | title = Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy | journal = Nature | volume = 477 | issue = 7362 | pages = 95–98 | year = 2011 | pmid = 21849975 | doi = 10.1038/nature10347 | bibcode = 2011Natur.477...95S | s2cid = 4409389 | url = https://resolver.caltech.edu/CaltechAUTHORS:20110922-140553274 }}</ref>