Relevance of the Entry by Fusion at the Cytoplasmic Membrane vs. Fusion After Endocytosis in the HIV and SARS-Cov-2 Infections.

Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 0173555 Publication Model: Print Cited Medium: Print ISSN: 0080-1844 (Print) Linking ISSN: 00801844 NLM ISO Abbreviation: Results Probl Cell Differ Subsets: MEDLINE

Original Publication: Berlin, New York, Springer-Verlag.

COVID-19*/metabolism ; Viruses* ; HIV Infections*/metabolism; Humans ; SARS-CoV-2 ; Endocytosis ; Cell Membrane/metabolism

HIV-1 and SARS-Cov-2 fuse at the cell surface or at endosomal compartments for entry into target cells; entry at the cell surface associates to productive infection, whereas endocytosis of low pH-independent viruses may lead to virus inactivation, slow replication, or alternatively, to productive infection. Endocytosis and fusion at the cell surface are conditioned by cell type-specific restriction factors and the presence of enzymes required for activation of the viral fusogen. Whereas fusion with the plasma membrane is considered the main pathway to productive infection of low pH-independent entry viruses, endocytosis is also productive and may be the main route of the highly efficient cell-to-cell dissemination of viruses. Alternative receptors, membrane cofactors, and the presence of enzymes processing the fusion protein at the cell membrane, determine the balance between fusion and endocytosis in specific target cells. Characterization of the mode of entry in particular cell culture conditions is desirable to better assess the effect of neutralizing and blocking agents and their mechanism of action. Whatever the pathway of virus internalization, production of the viral proteins into the cells can lead to the expression of the viral fusion protein on the cell surface; if this protein is able to induce membrane fusion at physiological pH, it promotes the fusion of the infected cell with surrounding uninfected cells, leading to the formation of syncytia or heterokaryons. Importantly, particular membrane proteins and lipids act as cofactors to support fusion. Virus-induced cell-cell fusion leads to efficient virus replication into fused cells, cell death, inflammation, and severe disease.
(© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Barad BA, Echols N, Wang RY-R, Cheng Y, DiMaio F, Adams PD, Fraser JS (2015) EMRinger: side chain–directed model and map validation for 3D cryo-electron microscopy. Nat Methods 12(10):943–946. (PMID: 26280328458948110.1038/nmeth.3541)
Beitari S, Pan Q, Finzi A, Liang C (2020) Differential pressures of SERINC5 and IFITM3 on HIV-1 envelope glycoprotein over the course of HIV-1 infection. J Virol 94(16):e00514–20. (PMID: 32493821739489310.1128/JVI.00514-20)
Blaak H, van’t Wout AB, Brouwer M, Hooibrink B, Hovenkamp E, Schuitemaker H (2000) In vivo HIV-1 infection of CD45RA+ CD4+ T cells is established primarily by syncytium-inducing variants and correlates with the rate of CD4+Tcell decline. Proc Natl Acad Sci 97(3):1269–1274. (PMID: 106555201559210.1073/pnas.97.3.1269)
Boge M, Wyss S, Bonifacino JS, Thali M (1998) A membrane-proximal tyrosine-based signal mediates internalization of the HIV-1 envelope glycoprotein via interaction with the AP-2 clathrin adaptor. J Biol Chem 273(25):15773–15778. (PMID: 962417610.1074/jbc.273.25.15773)
Bohan D, Van Ert H, Ruggio N, Rogers KJ, Badreddine M, Aguilar Briseño JA, Elliff JM, Rojas Chavez RA, Gao B, Stokowy T et al (2021) Phosphatidylserine receptors enhance SARS-Cov-2 infection. PLoS Pathog 17(11):e1009743. (PMID: 34797899864188310.1371/journal.ppat.1009743)
Boson B, Legros V, Zhou B, Siret E, Mathieu C, Cosset F-L, Lavillette D, Denolly S (2021) The SARS-Cov-2 envelope and membrane proteins modulate maturation and retention of the spike protein, allowing assembly of virus-like particles. J Biol Chem 296.
Braga L, Ali H, Secco I, Chiavacci E, Neves G, Goldhill D, Penn R, Jimenez-Guardeño JM, Ortega-Prieto AM, Bussani R et al (2021) Drugs that inhibit TMEM16 proteins block SARS-Cov-2 spike-induced syncytia. Nature 594(7861):88–93. (PMID: 33827113761105510.1038/s41586-021-03491-6)
Buchrieser J, Dufloo J, Hubert M, Monel B, Planas D, Rajah MM, Planchais C, Porrot F, Guivel-Benhassine F, Van der Werf S et al (2020) Syncytia formation by SARS-Cov-2-infected cells. EMBO J 39(23):e106267. (PMID: 33051876764602010.15252/embj.2020106267)
Bussani R, Schneider E, Zentilin L, Collesi C, Ali H, Braga L, Volpe MC, Colliva A, Zanconati F, Berlot G et al (2020) Persistence of viral RNA, pneumocyte syncytia and thrombosis are hallmarks of advanced COVID-19 pathology. EBioMedicine 61:103104. (PMID: 33158808767759710.1016/j.ebiom.2020.103104)
Byland R, Vance PJ, Hoxie JA, Marsh M (2007) A conserved dileucine motif mediates clathrin and AP-2–dependent endocytosis of the HIV-1 envelope protein. Mol Biol Cell 18(2):414–425. (PMID: 17108326178377110.1091/mbc.e06-06-0535)
Cameroni E, Bowen JE, Rosen LE, Saliba C, Zepeda SK, Culap K et al (2022) Broadly neutralizing antibodies overcome SARS-CoV-2 omicron antigenic shift. Nature 602(7898):664–670. (PMID: 3501619510.1038/s41586-021-04386-2)
Casado C, Marrero-Herna ́ndez S, Ma ́rquez-Arce D, Pernas M, Marfil S, Borra’s-Grañana F, Olivares I, Cabrera-Rodr ́ıguez R, Valera M-S, de Armas-Rillo L, Lemey P, Blanco J, Valenzuela-Fernández A, Lopez-Galíndez C (2018) Viral characteristics associated with the clinical nonprogressor phenotype are inherited by viruses from a cluster of HIV-1 elite controllers. MBio 9(2):e02338–17. (PMID: 29636433589388110.1128/mBio.02338-17)
Cantuti-Castelvetri L, Ojha R, Pedro LD, Djannatian M, Franz J, Kuivanen S, van der Meer F, Kallio K, Kaya T, Anastasina M, Smura T, Levanov L, Szirovicza L, Tobi A, Kallio-Kokko H, Österlund P, Joensuu M, Meunier FA, Butcher SJ, Winkler MS, Mollenhauer B, Helenius A, Gokce O, Teesalu T, Hepojoki J, Vapalahti O, Stadelmann C, Balistreri G, Simons M (2020) Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity Another host factor for SARSCoV-2. Science 370(6518):856–860. https://doi.org/10.1126/science.abd2985. (PMID: 10.1126/science.abd2985330822937857391)
Cattin-Ortolá J, Welch LG, Maslen SL, Papa G, James LC, Munro S (2021) Sequences in the cytoplasmic tail of SARS-Cov-2 spike facilitate expression at the cell surface and syncytia formation. Nat Commun 12(1):5333. (PMID: 34504087842965910.1038/s41467-021-25589-1)
Cavrois M, Neidleman J, Bigos M, Greene WC (2004) Fluorescence resonance energy transfer-based HIV-1 virion fusion assay. Flow Cytometry Protoc 263:333–343. (PMID: 10.1385/1-59259-773-4:333)
Clausen TM, Sandoval DR, Spliid CB, Pihl J, Perrett HR, Painter CD, Narayanan A, Majowicz SA, Kwong EM, McVicar RN et al (2020) SARS-Cov-2 infection depends on cellular heparan sulfate and ACE2. Cell 183(4):1043–1057. (PMID: 32970989748998710.1016/j.cell.2020.09.033)
Connell BJ, Hermans LE, Wensing AM, Schellens I, Schipper PJ, van Ham PM, de Jong DT, Otto S, Mathe T, Moraba R et al (2020) Immune activation correlates with and predicts CXCR4 co-receptor tropism switch in HIV-1 infection. Sci Rep 10(1):15866. (PMID: 32985522752299310.1038/s41598-020-71699-z)
Corver J, Broer R, Van Kasteren P, Spaan W (2009) Mutagenesis of the transmembrane domain of the SARS coronavirus spike glycoprotein: refinement of the requirements for SARS coronavirus cell entry. Virol J 6:1–13. (PMID: 10.1186/1743-422X-6-230)
Daly JL, Simonetti B, Klein K, Chen K-E, Williamson MK, Antón-Plágaro C, Shoemark DK, Simón-Gracia L, Bauer M, Hollandi R, Greber UF, Horvath P, Sessions RB, Helenius A, Hiscox JA, Teesalu T, Matthews DA, Davidson AD, Collins BM, Cullen PJ, Yamauchi Y (2020) Neuropilin-1 is a host factor for SARS-CoV-2 infection Another host factor for SARS-CoV-2. Science 370(6518):861–865. https://doi.org/10.1126/science.abd3072. (PMID: 10.1126/science.abd3072330822947612957)
Dimitrov D, Willey R, Sato H, Chang L-J, Blumenthal R, Martin M (1993) Quantitation of human immunodeficiency virus type 1 infection kinetics. J Virol 67(4):2182–2190. (PMID: 844572824033310.1128/jvi.67.4.2182-2190.1993)
Egan MA, Carruth LM, Rowell JF, Yu X, Siliciano RF (1996) Human immunodeficiency virus type 1 envelope protein endocytosis mediated by a highly conserved intrinsic internalization signal in the cytoplasmic domain of gp41 is suppressed in the presence of the pr55gag precursor protein. J Virol 70(10):6547–6556. (PMID: 879428919069510.1128/jvi.70.10.6547-6556.1996)
Fackler OT, Peterlin BM (2000) Endocytic entry of HIV-1. Curr Biol 10(16):1005–1008. (PMID: 1098539010.1016/S0960-9822(00)00654-0)
Fan Y, Li X, Zhang L et al (2022) SARS-CoV-2 omicron variant: recent progress and future perspectives. Signal Transduct Target Ther 7:141. (PMID: 35484110904746910.1038/s41392-022-00997-x)
Gu Y, Cao J, Zhang X, Gao H, Wang Y, Wang J, He J, Jiang X, Zhang J, Shen G et al (2022) Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-Cov-2. Cell Res 32(1):24–37. (PMID: 3483705910.1038/s41422-021-00595-6)
Han P, Li L, Liu S, Wang Q, Zhang D, Xu Z, Han P, Li X, Peng Q, Su C et al (2022) Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-Cov-2. Cell 185(4):630–640. (PMID: 35093192873327810.1016/j.cell.2022.01.001)
Hoffman HK, Aguilar RS, Clark AR, Groves NS, Pezeshkian N, Bruns MM, van Engelenburg SB (2022) Endocytosed HIV-1 envelope glycoprotein traffics to Rab14+ late endosomes and lysosomes to regulate surface levels in T-cell lines. J Virol 96(14):e00767–22. (PMID: 35770989932770310.1128/jvi.00767-22)
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu N-H, Nitsche A, Müller MA, Drosten C, Pöhlmann S (2020) SARS-Cov-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181(2):271–280.e8. (PMID: 32142651710262710.1016/j.cell.2020.02.052)
Hubner W, McNerney GP, Chen P, Dale BM, Gordon RE, Chuang FY, Li X-D, Asmuth DM, Huser T, Chen BK (2009) Quantitative 3D video microscopy of HIV transfer across T cell virological synapses. Science 323(5922):1743–1747. (PMID: 19325119275652110.1126/science.1167525)
Jackson CB, Farzan M, Chen B, Choe H (2022) Mechanisms of SARS-Cov-2 entry into cells. Nat Rev Mol Cell Biol 23(1):3–20. (PMID: 3461132610.1038/s41580-021-00418-x)
Jemielity S, Wang JJ, Chan YK, Ahmed AA, Li W, Monahan S, Bu X, Farzan M, Freeman GJ, Umetsu DT et al (2013) TIM-family proteins promote infection of multiple enveloped viruses through virion-associated phosphatidylserine. PLoS Pathog 9(3):e1003232. (PMID: 23555248361069610.1371/journal.ppat.1003232)
Klimstra WB, Tilston-Lunel NL, Nambulli S, Boslett J, McMillen CM, Gilliland T, Dunn MD, Sun C, Wheeler SE, Wells A et al (2020) SARS-Cov-2 growth, furin-cleavage-site adaptation and neutralization using serum from acutely infected hospitalized COVID-19 patients. J Gen Virol 101(11):1156. (PMID: 32821033787956110.1099/jgv.0.001481)
Lempp FA, Soriaga LB, Montiel-Ruiz M, Benigni F, Noack J, Park Y-J, Bianchi S, Walls AC, Bowen JE, Zhou J et al (2021) Lectins enhance SARS-Cov-2 infection and influence neutralizing antibodies. Nature 598(7880):342–347. (PMID: 3446495810.1038/s41586-021-03925-1)
Lu Q, Liu J, Zhao S, Castro MFG, Laurent-Rolle M, Dong J, Ran X, Damani-Yokota P, Tang H, Karakousi T et al (2021) SARS-Cov-2 exacerbates proinflammatory responses in myeloid cells through C-type lectin receptors and Tweety family member 2. Immunity 54(6):1304–1319. (PMID: 34048708810688310.1016/j.immuni.2021.05.006)
Majdoul S, Compton AA (2022) Lessons in self-defence: inhibition of virus entry by intrinsic immunity. Nat Rev Immunol 22(6):339–352. (PMID: 3464603310.1038/s41577-021-00626-8)
McBride CE, Machamer CE (2010) Palmitoylation of SARS-Cov S protein is necessary for partitioning into detergent-resistant membranes and cell–cell fusion but not interaction with m protein. Virology 405(1):139–148. (PMID: 2058005210.1016/j.virol.2010.05.031)
Melikyan GB (2014) HIV entry: a game of hide-and-fuse? Curr Opin Virol 4:1–7. (PMID: 2452528810.1016/j.coviro.2013.09.004)
Meng B, Abdullahi A, Ferreira IATM et al (2022) Altered TMPRSS2 usage by SARS-CoV-2 omicron impacts infectivity and fusogenicity. Nature 603:706–714. (PMID: 35104837894285610.1038/s41586-022-04474-x)
Ogle BM, Cascalho M, Platt JL (2005) Biological implications of cell fusion. Nat Rev Mol Cell Biol 6(7):567–575. https://doi.org/10.1038/nrm1678. (PMID: 10.1038/nrm167815957005)
Qi M, Williams JA, Chu H, Chen X, Wang J-J, Ding L, Akhirome E, Wen X, Lapierre LA, Goldenring JR et al (2013) Rab11-FIP1C and Rab14 direct plasma membrane sorting and particle incorporation of the HIV-1 envelope glycoprotein complex. PLoS Pathog 9(4):e1003278. (PMID: 23592992361698310.1371/journal.ppat.1003278)
Qu P, Evans JP, Kurhade C, Zeng C, Zheng Y-M, Xu K, Shi P-Y, Xie X, Liu S-L (2023) Determinants and mechanisms of the low fusogenicity and high dependence on endosomal entry of omicron subvariants. MBio 14(1):e03176–22. (PMID: 36625591997299710.1128/mbio.03176-22)
Rajah MM, Bernier A, Buchrieser J, Schwartz O (2022) The mechanism and consequences of SARS-Cov-2 spike-mediated fusion and syncytia formation. J Mol Biol 434(6):167280. (PMID: 3460683110.1016/j.jmb.2021.167280)
Rivera-Toledo E, Huerta L, Larralde C, Lamoyi E (2011) Quantitative and phenotypic analyses of lymphocyte–monocyte heterokaryons induced by the HIV envelope proteins: significant loss of lymphoid markers. Exp Mol Pathol 90(2):157–166. https://doi.org/10.1016/j.yexmp.2010.11.006. (PMID: 10.1016/j.yexmp.2010.11.00621110955)
Ruiz-Rivera MB, Gómez-Icazbalceta G, Lamoyi E, Huerta L (2021) Host membrane proteins in the HIV-induced membrane fusion: role in pathogenesis and therapeutic potential of autoantibodies. Curr Opin Pharmacol 60:241–248. (PMID: 3448133410.1016/j.coph.2021.07.005)
Sanders DW, Jumper CC, Ackerman PJ, Bracha D, Donlic A, Kim H, Kenney D, Castello-Serrano I, Suzuki S, Tamura T et al (2021) SARS-Cov-2 requires cholesterol for viral entry and pathological syncytia formation. elife 10:e65962. (PMID: 33890572810496610.7554/eLife.65962)
Schaeffer E, Soros VB, Greene WC (2004) Compensatory link between fusion and endocytosis of human immunodeficiency virus type 1 in human CD4 T lymphocytes. J Virol 78(3):1375–1383. (PMID: 1472229232136810.1128/JVI.78.3.1375-1383.2004)
Shen X-R, Geng R, Li Q, Chen Y, Li S-F, Wang Q, Min J, Yang Y, Li B, Jiang R-D et al (2022) ACE2-independent infection of T lymphocytes by SARS-Cov-2. Signal Transduct Target Ther 7(1):83. (PMID: 35277473891414310.1038/s41392-022-00919-x)
Shi G, Kenney AD, Kudryashova E, Zani A, Zhang L, Lai KK, Hall-Stoodley L, Robinson RT, Kudryashov DS, Compton AA et al (2021) Opposing activities of IFITM proteins in SARS-Cov-2 infection. EMBO J 40(3):e106501. (PMID: 3327092710.15252/embj.2020106501)
Stein BS, Gowda SD, Lifson JD, Penhallow RC, Bensch KG, Engleman EG (1987) Ph-independent HIV entry into CD4-positive T cells via virus envelope fusion to the plasma membrane. Cell 49(5):659–668. (PMID: 310783810.1016/0092-8674(87)90542-3)
Teesalu T, Sugahara KN, Kotamraju VR, Ruoslahti E (2009) C-end rule peptides mediate neuropilin-1-dependent cell vascular and tissue penetration. Proc Natl Acad Sci 106(38):16157–16162. (PMID: 19805273275254310.1073/pnas.0908201106)
Tian S, Hu W, Niu L, Liu H, Xu H, Xiao S et al (2020) Novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. J Thoracic Oncol 15(5):700–704. (PMID: 10.1016/j.jtho.2020.02.010)
Wang Q, Finzi A, Sodroski J (2020) The conformational states of the HIV-1 envelope glycoproteins. Trends Microbiol 28(8):655–667. (PMID: 32418859736354810.1016/j.tim.2020.03.007)
Wang X, Melino G, Shi Y (2021) Actively or passively deacidified lysosomes push 𝛽-coronavirus egress. Cell Death Dis 12(3):235. (PMID: 33664221793052310.1038/s41419-021-03501-5)
Whitlock JM, Chernomordik LV (2021) Flagging fusion: phosphatidylserine signaling in cell–cell fusion. J Biol Chem 296:100411. (PMID: 33581114800581110.1016/j.jbc.2021.100411)
Wu L, Zhou L, Mo M, Liu T, Wu C, Gong C, Lu K, Gong L, Zhu W, Xu Z (2022) SARS-Cov-2 omicron RBD shows weaker binding affinity than the currently dominant delta variant to human ACE2. Signal Transduct Target Ther 7(1):8. (PMID: 34987150872747510.1038/s41392-021-00863-2)
Xie Q, Bozzo CP, Eiben L, Noettger S, Kmiec D, Nchioua R, Niemeyer D, Volcic M, Lee JH, Zech F, Sparrer KMJ, Drosten C, Kirchhoff F (2023) Endogenous IFITMs boost SARS-coronavirus 1 and 2 replication whereas overexpression inhibits infection by relocalizing ACE2. iScience 26(4):106395. (PMID: 369680881000999710.1016/j.isci.2023.106395)
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang F-S (2020) Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 8:420–422. (PMID: 32085846716477110.1016/S2213-2600(20)30076-X)
Zaitseva E, Zaitsev E, Melikov K, Arakelyan A, Marin M, Villasmil R, Margolis LB, Melikyan GB, Chernomordik LV (2017) Fusion stage of HIV-1 entry depends on virus-induced cell surface exposure of phosphatidylserine. Cell Host Microbe 22(1):99–110. (PMID: 28704658555824110.1016/j.chom.2017.06.012)
Zeng C, Evans JP, King T, Zheng Y-M, Oltz EM, Whelan SP, Saif LJ, Peeples ME, Liu S-L (2022) SARS-Cov-2 spreads through cell-to-cell transmission. Proc Natl Acad Sci 119(1):e2111400119. (PMID: 3493769910.1073/pnas.2111400119)
Zhao X, Zheng S, Chen D, Zheng M, Li X, Li G, Lin H, Chang J, Zeng H, Guo J-T (2020) Ly6e restricts entry of human coronaviruses, including currently pandemic SARS-Cov-2. J Virol 94(18):e00562–20. (PMID: 32641482745956910.1128/JVI.00562-20)

Keywords: Endocytosis; Fusion; HIV; Lymphocytes; Pathogenicity; Plasma membrane; SARS-CoV-2; Syncytia; Transmissibility

Date Created: 20231123 Date Completed: 20231127 Latest Revision: 20231127

20231128

10.1007/978-3-031-37936-9_16

37996685