Editing HIV (section)

===Replication cycle===
{{update|section|date=February 2025}}
[[File:HIV-replication-cycle-en.svg|thumb|upright=1.8|The HIV replication cycle]]

====Entry to the cell====
[[File:HIV Membrane fusion panel.svg|thumb|upright=1.8|'''Mechanism of viral entry''': '''1.''' Initial interaction between gp120 and CD4. '''2.''' Conformational change in gp120 allows for secondary interaction with CXCR4. '''3.''' The distal tips of gp41 are inserted into the cellular membrane. '''4.''' gp41 undergoes significant conformational change; folding in half and forming coiled-coils. This process pulls the viral and cellular membranes together, fusing them.]]

The HIV virion enters [[macrophage]]s and CD4<SUP>+</SUP> [[T cells]] by the [[adsorption]] of [[glycoprotein]]s on its surface to receptors on the target cell followed by fusion of the [[viral envelope]] with the target cell membrane and the release of the HIV capsid into the cell.<ref name=Chan2>{{cite journal | vauthors = Chan DC, Kim PS | title = HIV entry and its inhibition | journal = Cell | volume = 93 | issue = 5 | pages = 681–4 | year = 1998 | pmid = 9630213 | doi = 10.1016/S0092-8674(00)81430-0 | s2cid = 10544941 | doi-access = free }}</ref><ref name=Wyatt>{{cite journal | vauthors = Wyatt R, Sodroski J | title = The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens | journal = Science | volume = 280 | issue = 5371 | pages = 1884–8 | year = 1998 | pmid = 9632381 | doi = 10.1126/science.280.5371.1884 | bibcode = 1998Sci...280.1884W }}</ref>

Entry to the cell begins through interaction of the trimeric envelope complex ([[gp160]] spike) on the HIV viral envelope and both [[CD4]] and a chemokine co-receptor (generally either [[CCR5]] or [[CXCR4]], but others are known to interact) on the target cell surface.<ref name=Chan2 /><ref name=Wyatt /> Gp120 binds to [[integrin]] α<sub>4</sub>β<sub>7</sub> activating [[LFA-1]], the central integrin involved in the establishment of [[virological synapse]]s, which facilitate efficient cell-to-cell spreading of HIV-1.<ref name=Arthos>{{cite journal | vauthors = Arthos J, Cicala C, Martinelli E, Macleod K, Van Ryk D, Wei D, Xiao Z, Veenstra TD, Conrad TP, Lempicki RA, McLaughlin S, Pascuccio M, Gopaul R, McNally J, Cruz CC, Censoplano N, Chung E, Reitano KN, Kottilil S, Goode DJ, Fauci AS | title = HIV-1 envelope protein binds to and signals through integrin alpha(4)beta(7), the gut mucosal homing receptor for peripheral T cells | journal = Nature Immunology | volume = 9| issue = 3 | pages = 301–9 | year = 2008 | pmid = 18264102 | doi = 10.1038/ni1566 | s2cid = 205361178 }}</ref> The gp160 spike contains binding domains for both CD4 and chemokine receptors.<ref name=Chan2 /><ref name=Wyatt />

The first step in fusion involves the high-affinity attachment of the CD4 binding domains of [[gp120]] to CD4. Once gp120 is bound with the CD4 protein, the envelope complex undergoes a structural change, exposing the chemokine receptor binding domains of gp120 and allowing them to interact with the target chemokine receptor.<ref name=Chan2 /><ref name=Wyatt /> This allows for a more stable two-pronged attachment, which allows the [[N-terminus|N-terminal]] fusion peptide gp41 to penetrate the cell membrane.<ref name=Chan2 /><ref name=Wyatt /> [[Repeated sequence (DNA)|Repeat sequences]] in gp41, HR1, and HR2 then interact, causing the collapse of the extracellular portion of gp41 into a hairpin shape. This loop structure brings the virus and cell membranes close together, allowing fusion of the membranes and subsequent entry of the viral capsid.<ref name=Chan2 /><ref name=Wyatt />

After HIV has bound to the target cell, the HIV RNA and various enzymes, including reverse transcriptase, integrase, ribonuclease, and protease, are injected into the cell.<ref name=Chan2 />{{Failed verification|date=April 2014}} During the [[microtubule]]-based transport to the nucleus, the viral single-strand RNA genome is transcribed into double-strand DNA, which is then integrated into a host chromosome.

HIV can infect [[dendritic cell]]s (DCs) by this CD4-CCR5 route, but another route using [[Mannose receptor|mannose-specific C-type lectin receptors]] such as [[DC-SIGN]] can also be used.<ref name=Pope_2003>{{cite journal | vauthors = Pope M, Haase AT | title = Transmission, acute HIV-1 infection and the quest for strategies to prevent infection | journal = Nature Medicine | volume = 9 | issue = 7 | pages = 847–52 | year = 2003 | pmid = 12835704 | doi = 10.1038/nm0703-847 | s2cid = 26570505 | doi-access = free }}</ref> DCs are one of the first cells encountered by the virus during sexual transmission. They are currently thought to play an important role by transmitting HIV to T cells when the virus is captured in the [[mucosa]] by DCs.<ref name=Pope_2003 /> The presence of [[FEZ-1]], which occurs naturally in [[neuron]]s, is believed to prevent the infection of cells by HIV.<ref>{{cite journal | vauthors = Haedicke J, Brown C, Naghavi MH | title = The brain-specific factor FEZ1 is a determinant of neuronal susceptibility to HIV-1 infection | journal = Proceedings of the National Academy of Sciences | volume = 106 | issue = 33 | pages = 14040–14045 | date = Aug 2009 | pmid = 19667186 | pmc = 2729016 | doi = 10.1073/pnas.0900502106 | bibcode = 2009PNAS..10614040H | doi-access = free }}</ref>

[[File:Itrafig2.jpg|thumb|left|[[Clathrin-mediated endocytosis]]]]
HIV-1 entry, as well as entry of many other retroviruses, has long been believed to occur exclusively at the plasma membrane. More recently, however, productive infection by [[pH]]-independent, [[clathrin-mediated endocytosis]] of HIV-1 has also been reported and was recently suggested to constitute the only route of productive entry.<ref>{{cite journal | vauthors = Daecke J, Fackler OT, Dittmar MT, Kräusslich HG | title = Involvement of clathrin-mediated endocytosis in human immunodeficiency virus type 1 entry | journal = Journal of Virology | volume = 79 | issue = 3 | pages = 1581–1594 | date = 2005 | pmid = 15650184 | pmc = 544101 | doi = 10.1128/jvi.79.3.1581-1594.2005 }}</ref><ref>{{cite journal | vauthors = Miyauchi K, Kim Y, Latinovic O, Morozov V, Melikyan GB | title = HIV Enters Cells via Endocytosis and Dynamin-Dependent Fusion with Endosomes | journal = Cell | volume = 137 | issue = 3 | pages = 433–444 | date = 2009 | pmid = 19410541 | pmc = 2696170 | doi = 10.1016/j.cell.2009.02.046 }}</ref><ref>{{cite journal | vauthors = Koch P, Lampe M, Godinez WJ, Müller B, Rohr K, Kräusslich HG, Lehmann MJ | title = Visualizing fusion of pseudotyped HIV-1 particles in real time by live cell microscopy | journal = Retrovirology | volume = 6 | pages =  84 | date = 2009 | pmid = 19765276 | pmc = 2762461 | doi = 10.1186/1742-4690-6-84 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Thorley JA, McKeating JA, Rappoport JZ | title = Mechanisms of viral entry: sneaking in the front door | journal = Protoplasma | volume = 244 | issue = 1–4 | pages = 15–24 | date = 2010 | pmid = 20446005 | pmc = 3038234 | doi = 10.1007/s00709-010-0152-6 }}</ref><ref>{{cite journal | vauthors = Permanyer M, Ballana E, Esté JA | title = Endocytosis of HIV: anything goes | journal = Trends in Microbiology | volume = 18 | issue = 12 | pages = 543–551 | date = 2010 | pmid = 20965729 | doi = 10.1016/j.tim.2010.09.003 }}</ref>

====Replication and transcription====
[[File:Reverse Transcription.png|thumb|[[Reverse transcription]] of the HIV [[genome]] into [[double-stranded DNA]]]]

Shortly after the viral capsid enters the cell, an [[enzyme]] called [[reverse transcriptase]] liberates the positive-sense single-stranded [[RNA]] genome from the attached viral proteins and copies it into a [[cDNA|complementary DNA]] (cDNA) molecule.<ref name=Zheng>{{cite journal | vauthors = Zheng YH, Lovsin N, Peterlin BM | title = Newly identified host factors modulate HIV replication | journal = Immunology Letters | volume = 97 | issue = 2 | pages = 225–34 | year = 2005 | pmid = 15752562 | doi = 10.1016/j.imlet.2004.11.026 }}</ref> The process of reverse transcription is extremely error-prone, and the resulting mutations may cause [[Resistance to antiviral drugs|drug resistance]] or allow the virus to evade the body's immune system. The reverse transcriptase also has ribonuclease activity that degrades the viral RNA during the synthesis of cDNA, as well as DNA-dependent DNA polymerase activity that creates a [[Sense (molecular biology)|sense]] DNA from the ''antisense'' cDNA.<ref>{{cite web |url=http://student.ccbcmd.edu/courses/bio141/lecguide/unit3/viruses/hivlc.html |website=Doc Kaiser's Microbiology Home Page |title=IV. Viruses> F. Animal Virus Life Cycles > 3. The Life Cycle of HIV |publisher=Community College of Baltimore County |date=January 2008 |url-status=dead |archive-url=https://web.archive.org/web/20100726222939/http://student.ccbcmd.edu/courses/bio141/lecguide/unit3/viruses/hivlc.html |archive-date=July 26, 2010 |df=mdy-all }}</ref> Together, the cDNA and its complement form a double-stranded viral DNA that is then transported into the [[cell nucleus]]. The integration of the viral DNA into the host cell's [[genome]] is carried out by another viral enzyme called [[integrase]].<ref name=Zheng />

The integrated viral DNA may then lie dormant, in the latent stage of HIV infection.<ref name=Zheng /> To actively produce the virus, certain cellular [[transcription factor]]s need to be present, the most important of which is [[NF-κB|NF-''κ''B]] (nuclear factor kappa&nbsp;B), which is upregulated when T cells become activated.<ref name=Hiscott>{{cite journal | vauthors = Hiscott J, Kwon H, Génin P | title = Hostile takeovers: viral appropriation of the NF-kB pathway | journal = Journal of Clinical Investigation | volume = 107 | issue = 2 | pages = 143–151 | year = 2001 | pmid = 11160127 | pmc = 199181 | doi = 10.1172/JCI11918 }}</ref> This means that those cells most likely to be targeted, entered and subsequently killed by HIV are those actively fighting infection.

During viral replication, the integrated DNA [[provirus]] is [[Transcription (genetics)|transcribed]] into RNA. The full-length genomic RNAs (gRNA) can be packaged into new viral particles in a [[pseudodiploid]] form. The selectivity in the packaging is explained by the structural properties of the dimeric conformer of the gRNA. The gRNA dimer is characterized  by a tandem three-way junction within the gRNA monomer, in which the SD and AUG [[Stem-loop|hairpins]], responsible for splicing and translation respectively, are sequestered and the DIS (dimerization initiation signal) hairpin is exposed. The formation of the gRNA dimer is mediated by a 'kissing'  interaction between the DIS hairpin loops of the gRNA monomers. At the same time, certain guanosine residues in the gRNA are made available for binding of the nucleocapsid (NC) protein leading to the subsequent virion assembly.<ref>{{Cite journal|last1=Keane|first1=Sarah C.|last2=Heng|first2=Xiao|last3=Lu|first3=Kun|last4=Kharytonchyk|first4=Siarhei|last5=Ramakrishnan|first5=Venkateswaran|last6=Carter|first6=Gregory|last7=Barton|first7=Shawn|last8=Hosic|first8=Azra|last9=Florwick|first9=Alyssa|last10=Santos|first10=Justin|last11=Bolden|first11=Nicholas C.|date=2015-05-22|title=Structure of the HIV-1 RNA packaging signal|url=http://dx.doi.org/10.1126/science.aaa9266|journal=Science|volume=348|issue=6237|pages=917–921|doi=10.1126/science.aaa9266|pmid=25999508|pmc=4492308|bibcode=2015Sci...348..917K|issn=0036-8075}}</ref> The labile gRNA dimer has been also reported to achieve a more stable conformation following the NC binding, in which both the DIS and the U5:AUG regions of the gRNA participate in extensive base pairing.<ref>{{Cite journal|last1=Keane|first1=Sarah C.|last2=Van|first2=Verna|last3=Frank|first3=Heather M.|last4=Sciandra|first4=Carly A.|last5=McCowin|first5=Sayo|last6=Santos|first6=Justin|last7=Heng|first7=Xiao|last8=Summers|first8=Michael F.|date=2016-10-10|title=NMR detection of intermolecular interaction sites in the dimeric 5′-leader of the HIV-1 genome|journal=Proceedings of the National Academy of Sciences|volume=113|issue=46|pages=13033–13038|doi=10.1073/pnas.1614785113|pmid=27791166|pmc=5135362|bibcode=2016PNAS..11313033K |issn=0027-8424|doi-access=free}}</ref>

RNA can also be [[post-transcriptional modification|processed]] to produce mature [[messenger RNA]]s (mRNAs). In most cases, this processing involves [[RNA splicing]] to produce mRNAs that are shorter than the full-length genome. Which part of the RNA is removed during RNA splicing determines which of the HIV protein-coding sequences is translated.<ref name="Ocwieja">{{cite journal | vauthors = Ocwieja KE, Sherrill-Mix S, Mukherjee R, Custers-Allen R, David P, Brown M, Wang S, Link DR, Olson J, Travers K, Schadt E, Bushman FD | display-authors = 6 | title = Dynamic regulation of HIV-1 mRNA populations analyzed by single-molecule enrichment and long-read sequencing | journal = Nucleic Acids Research | volume = 40 | issue = 20 | pages = 10345–55 | date = November 2012 | pmid = 22923523 | pmc = 3488221 | doi = 10.1093/nar/gks753 | url = https://academic.oup.com/nar/article/40/20/10345/2414624 }}</ref>

Mature HIV mRNAs are exported from the nucleus into the [[cytoplasm]], where they are [[Translation (genetics)|translated]] to produce HIV proteins, including [[Rev (HIV)|Rev]]. As the newly produced Rev protein is produced it moves to the nucleus, where it binds to full-length, unspliced copies of virus RNAs and allows them to leave the nucleus.<ref name=Pollard>{{cite journal | vauthors = Pollard VW, Malim MH | title = The HIV-1 Rev protein | journal = Annual Review of Microbiology | volume = 52 | pages = 491–532 | year = 1998 | pmid = 9891806 | doi = 10.1146/annurev.micro.52.1.491 }}</ref> Some of these full-length RNAs function as mRNAs that are translated to produce the structural proteins Gag and Env. Gag proteins bind to copies of the virus RNA genome to package them into new virus particles.<ref>{{cite journal | vauthors = Butsch M, Boris-Lawrie K | title = Destiny of unspliced retroviral RNA: ribosome and/or virion? | journal = Journal of Virology | volume = 76 | issue = 7 | pages = 3089–94 | date = April 2002 | pmid = 11884533 | pmc = 136024 | doi = 10.1128/JVI.76.7.3089-3094.2002 }}</ref>
HIV-1 and HIV-2 appear to package their RNA differently.<ref>{{cite journal | vauthors = Hellmund C, Lever AM | title = Coordination of Genomic RNA Packaging with Viral Assembly in HIV-1 | journal = Viruses | volume = 8 | issue = 7 | pages = 192 | date = July 2016 | pmid = 27428992 | pmc = 4974527 | doi = 10.3390/v8070192 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Soto-Rifo R, Limousin T, Rubilar PS, Ricci EP, Décimo D, Moncorgé O, Trabaud MA, André P, Cimarelli A, Ohlmann T | display-authors = 6 | title = Different effects of the TAR structure on HIV-1 and HIV-2 genomic RNA translation | journal = Nucleic Acids Research | volume = 40 | issue = 6 | pages = 2653–67 | date = March 2012 | pmid = 22121214 | pmc = 3315320 | doi = 10.1093/nar/gkr1093 }}</ref> HIV-1 will bind to any appropriate RNA.<ref>{{Cite book|url=https://books.google.com/books?id=P3vQCgAAQBAJ&q=HIV-1+will+bind+to+any+appropriate+RNA&pg=PA51|title=Role of Lipids in Virus Assembly| vauthors = Saad JS, Muriaux DM |date=2015-07-28|publisher=Frontiers Media SA|isbn=978-2-88919-582-4|language=en}}</ref> HIV-2 will preferentially bind to the mRNA that was used to create the Gag protein itself.<ref>{{cite journal | vauthors = Ricci EP, Herbreteau CH, Decimo D, Schaupp A, Datta SA, Rein A, Darlix JL, Ohlmann T | display-authors = 6 | title = In vitro expression of the HIV-2 genomic RNA is controlled by three distinct internal ribosome entry segments that are regulated by the HIV protease and the Gag polyprotein | journal = RNA | volume = 14 | issue = 7 | pages = 1443–55 | date = July 2008 | pmid = 18495939 | pmc = 2441975 | doi = 10.1261/rna.813608 }}</ref>

====Recombination====
{{Further|Genetic recombination}}
Two RNA genomes are encapsidated in each HIV-1 particle (see [[Structure and genome of HIV]]). Upon infection and replication catalyzed by reverse transcriptase, recombination between the two genomes can occur.<ref name="Hu">{{cite journal | vauthors = Hu WS, Temin HM | title = Retroviral recombination and reverse transcription | journal = Science | volume = 250 | issue = 4985 | pages = 1227–33 | year = 1990 | pmid = 1700865 | doi = 10.1126/science.1700865 | bibcode = 1990Sci...250.1227H }}</ref><ref name="Charpentier">{{cite journal | vauthors = Charpentier C, Nora T, Tenaillon O, Clavel F, Hance AJ | title = Extensive recombination among human immunodeficiency virus type 1 quasispecies makes an important contribution to viral diversity in individual patients | journal = Journal of Virology | volume = 80 | issue = 5 | pages = 2472–82 | year = 2006 | pmid = 16474154 | pmc = 1395372 | doi = 10.1128/JVI.80.5.2472-2482.2006 }}</ref> Recombination occurs as the single-strand, positive-sense RNA genomes are reverse transcribed to form DNA. During reverse transcription, the nascent DNA can switch multiple times between the two copies of the viral RNA. This form of recombination is known as copy-choice. Recombination events may occur throughout the genome. Anywhere from two to 20 recombination events per genome may occur at each replication cycle, and these events can rapidly shuffle the genetic information that is transmitted from parental to progeny genomes.<ref name="Charpentier" />

Viral recombination produces genetic variation that likely contributes to the [[evolution]] of resistance to [[Management of HIV/AIDS|anti-retroviral therapy]].<ref>{{cite journal | vauthors = Nora T, Charpentier C, Tenaillon O, Hoede C, Clavel F, Hance AJ | title = Contribution of recombination to the evolution of human immunodeficiency viruses expressing resistance to antiretroviral treatment | journal = Journal of Virology | volume = 81 | issue = 14 | pages = 7620–8 | year = 2007 | pmid = 17494080 | pmc = 1933369 | doi = 10.1128/JVI.00083-07 }}</ref> Recombination may also contribute, in principle, to overcoming the immune defenses of the host. Yet, for the adaptive advantages of genetic variation to be realized, the two viral genomes packaged in individual infecting virus particles need to have arisen from separate progenitor parental viruses of differing genetic constitution. It is unknown how often such mixed packaging occurs under natural conditions.<ref>{{cite journal | vauthors = Chen J, Powell D, Hu WS | title = High frequency of genetic recombination is a common feature of primate lentivirus replication | journal = Journal of Virology | volume = 80 | issue = 19 | pages = 9651–8 | year = 2006 | pmid = 16973569 | pmc = 1617242 | doi = 10.1128/JVI.00936-06 }}</ref>

Bonhoeffer ''et al.''<ref name=Bonhoeffer>{{cite journal | vauthors = Bonhoeffer S, Chappey C, Parkin NT, Whitcomb JM, Petropoulos CJ | title = Evidence for positive epistasis in HIV-1 | journal = Science | volume = 306 | issue = 5701 | pages = 1547–50 | year = 2004 | pmid = 15567861 | doi = 10.1126/science.1101786 | bibcode = 2004Sci...306.1547B | s2cid = 45784964 }}</ref> suggested that template switching by reverse transcriptase acts as a repair process to deal with breaks in the single-stranded RNA genome. In addition, Hu and Temin<ref name=Hu /> suggested that recombination is an adaptation for repair of damage in the RNA genomes. Strand switching (copy-choice recombination) by reverse transcriptase could generate an undamaged copy of genomic DNA from two damaged single-stranded RNA genome copies. This view of the adaptive benefit of recombination in HIV could explain why each HIV particle contains two complete genomes, rather than one. Furthermore, the view that recombination is a repair process implies that the benefit of repair can occur at each replication cycle, and that this benefit can be realized whether or not the two genomes differ genetically. On the view that recombination in HIV is a repair process, the generation of recombinational variation would be a consequence, but not the cause of, the evolution of template switching.<ref name=Bonhoeffer />

HIV-1 infection causes [[chronic inflammation]] and production of [[reactive oxygen species]].<ref>{{cite journal | vauthors = Israël N, Gougerot-Pocidalo MA | title = Oxidative stress in human immunodeficiency virus infection | journal = Cellular and Molecular Life Sciences | volume = 53 | issue = 11–12 | pages = 864–70 | year = 1997 | pmid = 9447238 | doi = 10.1007/s000180050106 | s2cid = 22663454 | pmc = 11147326 }}</ref> Thus, the HIV genome may be vulnerable to [[oxidative damage]], including breaks in the single-stranded RNA. For HIV, as well as for viruses in general, successful infection depends on overcoming host defense strategies that often include production of genome-damaging reactive oxygen species. Thus, Michod ''et al.''<ref name="pmid18295550">{{cite journal | vauthors = Michod RE, Bernstein H, Nedelcu AM | title = Adaptive value of sex in microbial pathogens | journal = Infection, Genetics and Evolution | volume = 8 | issue = 3 | pages = 267–85 | date = May 2008 | pmid = 18295550 | doi = 10.1016/j.meegid.2008.01.002 | bibcode = 2008InfGE...8..267M | url = http://www.hummingbirds.arizona.edu/Faculty/Michod/Downloads/IGE%20review%20sex.pdf | access-date = May 10, 2013 | archive-date = May 16, 2017 | archive-url = https://web.archive.org/web/20170516235741/http://www.hummingbirds.arizona.edu/Faculty/Michod/Downloads/IGE%20review%20sex.pdf | url-status = dead }}</ref> suggested that recombination by viruses is an adaptation for repair of genome damage, and that recombinational variation is a byproduct that may provide a separate benefit.

====Assembly and release====
[[File:HIV on macrophage.png|thumb|right|HIV assembling on the [[Cell membrane|surface]] of an infected [[macrophage]]. The HIV virions have been marked with a green [[fluorescent tag]] and then viewed under a fluorescent microscope.]]
The final step of the viral cycle, assembly of new HIV-1 virions, begins at the [[plasma membrane]] of the host cell. The Env polyprotein (gp160) goes through the [[endoplasmic reticulum]] and is transported to the [[Golgi apparatus]] where it is [[Bond cleavage|cleaved]] by [[furin]] resulting in the two HIV envelope glycoproteins, [[gp41]] and [[gp120]].<ref>{{cite journal | vauthors = Hallenberger S, Bosch V, Angliker H, Shaw E, Klenk HD, Garten W | title = Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160 | journal = Nature | volume = 360 | issue = 6402 | pages = 358–61 | date = November 26, 1992 | pmid = 1360148 | doi = 10.1038/360358a0 | bibcode = 1992Natur.360..358H | s2cid = 4306605 }}</ref> These are transported to the plasma membrane of the host cell where gp41 anchors gp120 to the membrane of the infected cell. The Gag (p55) and Gag-Pol (p160) polyproteins also associate with the inner surface of the plasma membrane along with the HIV genomic RNA as the forming virion begins to bud from the host cell. The budded virion is still immature as the [[Group-specific antigen|gag]] polyproteins still need to be cleaved into the actual matrix, capsid and nucleocapsid proteins. This cleavage is mediated by the packaged viral protease and can be inhibited by antiretroviral drugs of the [[Protease inhibitor (pharmacology)|protease inhibitor]] class. The various structural components then assemble to produce a mature HIV virion.<ref name=Gelderblom>{{cite book | author= Gelderblom HR | year = 1997 | title = HIV sequence compendium | chapter = Fine structure of HIV and SIV |chapter-url=http://www.hiv.lanl.gov/content/sequence/HIV/COMPENDIUM/1997/partIII/Gelderblom.pdf | editor = Los Alamos National Laboratory | pages = 31–44 | publisher = [[Los Alamos National Laboratory]] }}</ref> Only mature virions are then able to infect another cell.