CoChat
Sign Up
Cited by 45HIV Research and TreatmentCellular transport and secretionHIV/AIDS drug development and treatment

The Race against Protease Activation Defines the Role of ESCRTs in HIV Budding

Open access
Bendjennat, Mourad, Saffarian, Saveez·2016·PLOS Pathogens
DOI 10.1371/journal.ppat.1005657PMC PMC4900648
Open this paper in CoChat — free accountOpen PDF

Abstract

HIV virions assemble on the plasma membrane and bud out of infected cells using interactions with endosomal sorting complexes required for transport (ESCRTs). HIV protease activation is essential for maturation and infectivity of progeny virions, however, the precise timing of protease activation and its relationship to budding has not been well defined. We show that compromised interactions with ESCRTs result in delayed budding of virions from host cells. Specifically, we show that Gag mutants with compromised interactions with ALIX and Tsg101, two early ESCRT factors, have an average budding delay of ~75 minutes and ~10 hours, respectively. Virions with inactive proteases incorporated the full Gag-Pol and had ~60 minutes delay in budding. We demonstrate that during budding delay, activated proteases release critical HIV enzymes back to host cytosol leading to production of non-infectious progeny virions. To explain the molecular mechanism of the observed budding delay, we modulated the Pol size artificially and show that virion release delays are size-dependent and also show size-dependency in requirements for Tsg101 and ALIX. We highlight the sensitivity of HIV to budding "on-time" and suggest that budding delay is a potent mechanism for inhibition of infectious retroviral release.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.ppat.1005657

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Budding particles are often arrested with large cytoplasmic opening when one or both L domains are deleted, causing delays in maturation up to 10 h.

    “budding particles are also often arrested with a large cytoplasmic opening when one or both L domains are deleted, causing significant delays in their maturation up to 10 h [45].”

    From Budding of a Retrovirus: Some Assemblies Required (2020) · cites this paper as [45]

    The Introduction and Discussion report transient late-budding arrest after late-domain mutations and a release delay of about 10 hours for ΔPTAP Gag-Pol particles, versus about 70–75 minutes for ΔYP particles. The Discussion describes delayed closure of a large budding neck, but the 10-hour figure measures delayed budding or release, not delayed maturation; the paper instead reports defective maturation and loss of viral enzymes. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • L domains encoded by retroviral Gag are critical for proper packaging of Gag-Pol polyprotein.

    “It has been known for over two decades that the L domains encoded by the retroviral Gag polyprotein are critical for the proper packaging of the essential viral processing enzymes required for maturation and infectivity, known as the Gag-Pol polyprotein [43,44,45].”

    From Budding of a Retrovirus: Some Assemblies Required (2020) · cites this paper as [45]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 69

  1. [1]Debouck C, Gorniak JG, Strickler JE, Meek TD, Metcalf BW, Rosenberg M. Human immunodeficiency virus protease expressed in Escherichia coli exhibits autoprocessing and specific maturation of the gag precursor. Proc Natl Acad Sci U S A. 1987; 84: 8903– 8906. 3321060 PMC299659
  2. [2]Thompson MA, Aberg JA, Hoy JF, Telenti A, Benson C, Cahn P, Eron JJ, Günthard HF, Hammer SM, Reiss P, Richman DD, Rizzardini G, Thomas DL, Jacobsen DM, Volberding PA. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the international antiviral society–USA panel. JAMA. 2012; 308: 387– 402. 10.1001/jama.2012.7961 22820792 · DOI
  3. [3]Wlodawer A, Vondrasek J. INHIBITORS OF HIV-1 PROTEASE: A Major Success of Structure-Assisted Drug Design. Annual Review of Biophysics and Biomolecular Structure. 1998; 27: 249– 284. 9646869
  4. [4]Lee SK, Potempa M, Swanstrom R. The Choreography of HIV-1 Proteolytic Processing and Virion Assembly. J Biol Chem. 2012; 287: 40867– 40874. 10.1074/jbc.R112.399444 23043111 PMC3510790 · DOI
  5. [5]Göttlinger HG, Dorfman T, Sodroski JG, Haseltine WA. Effect of mutations affecting the p6 gag protein on human immunodeficiency virus particle release. Proc Natl Acad Sci U S A. 1991; 88: 3195– 3199. 2014240 PMC51412
  6. [6]Huang M, Orenstein JM, Martin MA, Freed EO. p6Gag is required for particle production from full-length human immunodeficiency virus type 1 molecular clones expressing protease. J Virol. 1995; 69: 6810– 6818. 7474093 PMC189593
  7. [7]Sundquist WI, Kräusslich HG. HIV-1 assembly, budding, and maturation. Cold Spring Harb Perspect Med. 2012; 2: a006924 10.1101/cshperspect.a006924 22762019 PMC3385941 · DOI · Paper page
  8. [9]Swanstrom R, Wills JW. Synthesis, assembly, and processing of viral proteins Cold Spring Harbor Laboratory Press 1997; 10 Skyline Drive, Plainview, New York 11803, USA. 21433349
  9. [10]Agniswamy J, Sayer JM, Weber IT, Louis JM. Terminal Interface Conformations Modulate Dimer Stability Prior to Amino Terminal Autoprocessing of HIV-1 Protease. Biochemistry. 2012; 51: 1041– 1050. 10.1021/bi201809s 22242794 PMC3287067 · DOI
  10. [11]Louis JM, Clore GM, Gronenborn AM. Autoprocessing of HIV-1 protease is tightly coupled to protein folding. Nat Struct Mol Biol. 1999; 6: 868– 875. 10467100
  11. [12]Louis JM, Nashed NT, Parris KD, Kimmel AR, Jerina DM. Kinetics and Mechanism of Autoprocessing of Human Immunodeficiency Virus Type 1 Protease from an Analog of the Gag-Pol Polyprotein. Proc Natl Acad Sci U S A. 1994; 91: 7970– 7974. 8058744 PMC44526
  12. [13]Erickson-Viitanen S, Manfredi J, Viitanen P, Tribe D, Tritch R, Hutchison C, Loeb D, Swanstrom R. Cleavage of HIV-1 gag polyprotein synthesized in vitro: sequential cleavage by the viral protease. AIDS Res Hum Retroviruses. 1989; 5: 577– 591. 2692658
  13. [14]Pettit S, Lindquist J, Kaplan A, Swanstrom R. Processing sites in the human immunodeficiency virus type 1 (HIV-1) Gag-Pro-Pol precursor are cleaved by the viral protease at different rates. Retrovirology. 2005; 2: 66 16262906 PMC1291402
  14. [15]Votteler J, Sundquist WI. Virus Budding and the ESCRT Pathway. Cell Host & Microbe. 2013; 14: 232– 241. 24034610 PMC3819203
  15. [16]Dores MR, Chen B, Lin H, Soh UJK, Paing MM, Montagne WA, Meerloo T, Trejo J. ALIX binds a YPX3L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting. J Cell Biol. 2012; 197: 407– 419. 10.1083/jcb.201110031 22547407 PMC3341166 · DOI
  16. [17]Carlton JG, Martin-Serrano J. Parallels Between Cytokinesis and Retroviral Budding: A Role for the ESCRT Machinery. Science. 2007; 316: 1908– 1912. 17556548
  17. [18]Lee HH, Elia N, Ghirlando R, Lippincott-Schwartz J, Hurley JH. Midbody Targeting of the ESCRT Machinery by a Noncanonical Coiled Coil in CEP55. Science. 2008; 322: 576– 580. 10.1126/science.1162042 18948538 PMC2720046 · DOI
  18. [19]Morita E, Sandrin V, Chung HY, Morham SG, Gygi SP, Rodesch CK, Sundquist WI. Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis. EMBO J. 2007; 26: 4215– 4227. 17853893 PMC2230844
  19. [21]Jimenez AJ, Maiuri P, Lafaurie-Janvore J, Divoux S, Piel M, Perez F. ESCRT Machinery Is Required for Plasma Membrane Repair. Science. 2014; 343: 1247136 10.1126/science.1247136 24482116 · DOI
  20. [22]Bieniasz PD. Late budding domains and host proteins in enveloped virus release. Virology 50th Anniversary Issue. 2006; 344: 55– 63. 16364736
  21. [23]Demirov DG, Freed EO. Retrovirus budding Virus Res. 2004; 106: 87– 102. 15567490
  22. [24]Morita E, Sundquist WI. Retrovirus budding. Annual Review of Cell and Develop Biology. 2004; 20: 395– 425. 15473846
  23. [25]Demirov DG, Ono A, Orenstein JM, Freed EO. Overexpression of the N-terminal domain of TSG101 inhibits HIV-1 budding by blocking late domain function. Proc Natl Acad Sci U S A. 2002; 99: 955– 960. 11805336 PMC117412
  24. [26]Garrus JE, von Schwedler UK, Pornillos OW, Morham SG, Zavitz KH, Wang HE, Wettstein DA, Stray KM, Côté M, Rich RL, et al Tsg101 and the Vacuolar Protein Sorting Pathway Are Essential for HIV-1 Budding. Cell. 2001; 107: 55– 65. 11595185
  25. [27]Martin-Serrano J, Zang T, Bieniasz PD. HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress. Nat Med. 2001; 7: 1313– 1319. 11726971
  26. [28]VerPlank L, Bouamr F, LaGrassa TJ, Agresta B, Kikonyogo A, Leis J, Carter CA. Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, binds the L domain in HIV type 1 Pr55Gag. Proc Natl Acad Sci U S A. 2001; 98: 7724– 7729. 11427703 PMC35409
  27. [29]Martin-Serrano J, Yaravoy A, Perez-Caballero D, Bieniasz PD. Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins. Proc Natl Acad Sci U S A. 2003; 100: 12414– 12419. 14519844 PMC218772
  28. [31]Strack B, Calistri A, Craig S, Popova E, Göttlinger HG. AIP1/ALIX Is a Binding Partner for HIV-1 p6 and EIAV p9 Functioning in Virus Budding. Cell. 2003; 114: 689– 699. 14505569
  29. [32]Vincent O, Rainbow L, Tilburn J, Arst J, Herbert N, Peñalva MA. YPXL/I Is a Protein Interaction Motif Recognized by Aspergillus PalA and Its Human Homologue, AIP1/ALIX. Mol Cell Biol. 2003; 23: 1647– 1655. 12588984 PMC151718
  30. [33]von Schwedler UK, Stuchell M, Müller B, Ward DM, Chung HY, Morita E, Wang HE, Davis T, He GP, Cimbora DM, et al The Protein Network of HIV Budding. Cell. 2003; 114: 701– 713. 14505570
  31. [34]Dussupt V, Javid MP, Abou-Jaoudé G, Jadwin JA, de La Cruz J, Nagashima K, Bouamr F. The Nucleocapsid Region of HIV-1 Gag Cooperates with the PTAP and LYPXnL Late Domains to Recruit the Cellular Machinery Necessary for Viral Budding. PLoS Pathog. 2009; 5: e1000339 10.1371/journal.ppat.1000339 19282983 PMC2651531 · DOI · Paper page
  32. [35]Popov S, Popova E, Inoue M, Göttlinger HG. Human Immunodeficiency Virus Type 1 Gag Engages the Bro1 Domain of ALIX/AIP1 through the Nucleocapsid. J Virol. 2008; 82: 1389– 1398. 18032513 PMC2224418
  33. [36]Craven RC, Harty RN, Paragas J, Palese P, Wills JW. Late Domain Function Identified in the Vesicular Stomatitis Virus M Protein by Use of Rhabdovirus-Retrovirus Chimeras. J Virol. 1999; 73: 3359– 3365. 10074190 PMC104100
  34. [37]Jayakar HR, Murti KG, Whitt MA. Mutations in the PPPY Motif of Vesicular Stomatitis Virus Matrix Protein Reduce Virus Budding by Inhibiting a Late Step in Virion Release. J Virol. 2000; 74: 9818– 9827. 11024108 PMC102018
  35. [38]Gheysen D, Jacobs E, de Foresta F, Thiriart C, Francotte M, Thines D, De Wilde M. Assembly and release of HIV-1 precursor Pr55gag virus-like particles from recombinant baculovirus-infected insect cells. Cell. 1989; 59: 103– 112. 2676191
  36. [39]Dussupt V, Sette P, Bello NF, Javid MP, Nagashima K, Bouamr F. Basic Residues in the Nucleocapsid Domain of Gag Are Critical for Late Events of HIV-1 Budding. J Virol. 2011; 85: 2304– 2315. 10.1128/JVI.01562-10 21159863 PMC3067763 · DOI · Paper page
  37. [40]Zhou W, Parent LJ, Wills JW, Resh MD. Identification of a membrane-binding domain within the amino-terminal region of human immunodeficiency virus type 1 Gag protein which interacts with acidic phospholipids. J Virol. 1994; 68: 2556– 2569. 8139035 PMC236733
  38. [41]Van Engelenburg SB, Shtengel G, Sengupta P, Waki K, Jarnik M, Ablan SD, Freed EO, Hess HF, Lippincott-Schwartz J (2014) Distribution of ESCRT Machinery at HIV Assembly Sites Reveals Virus Scaffolding of ESCRT Subunits. Science 343: 653– 656. 10.1126/science.1247786 24436186 PMC4791044 · DOI
  39. [42]Darke PL, Leu CT, Davis LJ, Heimbach JC, Diehl RE, Hill WS, Dixon RA, Sigal IS. Human immunodeficiency virus protease. Bacterial expression and characterization of the purified aspartic protease. J Biol Chem. 1989; 264: 2307– 2312. 2644259
  40. [43]Gillespie DT. Exact stochastic simulation of coupled chemical reactions. J Phys Chem. 1977; 81: 2340– 2361.
  41. [44]Fisher RD, Chung HY, Zhai Q, Robinson H, Sundquist WI, Hill CP. Structural and Biochemical Studies of ALIX/AIP1 and Its Role in Retrovirus Budding. Cell. 2007; 128: 841– 852. 17350572
  42. [46]Ako-Adjei D, Johnson MC, Vogt VM. The Retroviral Capsid Domain Dictates Virion Size, Morphology, and Coassembly of Gag into Virus-Like Particles. J Virol. 2005; 79: 13463– 13472. 16227267 PMC1262573
  43. [47]Gan X, Gould SJ. HIV Pol Inhibits HIV Budding and Mediates the Severe Budding Defect of Gag-Pol. PLoS ONE. 2012; 7: e29421 10.1371/journal.pone.0029421 22235295 PMC3250436 · DOI
  44. [48]Norgan AP, Lee JRE, Oestreich AJ, Payne JA, Krueger EW, Katzmann DJ. ESCRT-Independent Budding of HIV-1 Gag Virus-Like Particles from Saccharomyces cerevisiae Spheroplasts. PLoS ONE. 2012; 7: e52603 10.1371/journal.pone.0052603 23285107 PMC3528670 · DOI
  45. [49]Wilk T, Gross I, Gowen BE, Rutten T, de Haas F, Welker R, Kräusslich HG, Boulanger P, Fuller SD. Organization of Immature Human Immunodeficiency Virus Type 1. J Virol. 2001; 75: 759– 771. 11134289 PMC113972
  46. [50]Hanson PI, Roth R, Lin Y, Heuser JE. Plasma membrane deformation by circular arrays of ESCRT-III protein filaments. J Cell Biol. 2008; 180: 389– 402. 10.1083/jcb.200707031 18209100 PMC2213594 · DOI · Paper page
  47. [51]Hurley JH, Hanson PI. Membrane budding and scission by the ESCRT machinery: it's all in the neck. Nat. Rev. Mol Cell Biol. 2010; 11: 556– 566. 10.1038/nrm2937 20588296 PMC2922035 · DOI
  48. [52]Martin-Serrano J, Neil SJD. Host factors involved in retroviral budding and release. Nat Rev Micro. 2011; 9: 519– 531. 21677686
  49. [53]Prescher J, Baumgärtel V, Ivanchenko S, Torrano AA, Bräuchle C, Müller B, Lamb DC (2015) Super-Resolution Imaging of ESCRT-Proteins at HIV-1 Assembly Sites. PLoS Pathog. 11: e1004677 10.1371/journal.ppat.1004677 25710462 PMC4339578 · DOI
  50. [54]Bleck M, Itano MS, Johnson DS, Thomas VK, North AJ, Bieniasz PD, Simon SM (2014) Temporal and spatial organization of ESCRT protein recruitment during HIV-1 budding. Proceedings of the National Academy of Sciences. 111: 12211– 12216. PMC4142993 25099357
  51. [55]Morita E, Sandrin V, McCullough J, Katsuyama A, Baci Hamilton I, Sundquist WI. ESCRT-III Protein Requirements for HIV-1 Budding. Cell Host & Microbe. 2011; 9: 235– 242. 21396898 PMC3070458
  52. [56]Lee I-H, Kai H, Carlson L-A, Groves JT, Hurley JH. Negative membrane curvature catalyzes nucleation of endosomal sorting complex required for transport (ESCRT)-III assembly. Proc Natl Acad Sci U S A. 2015; 112; 15892– 15897. 10.1073/pnas.1518765113 26668364 PMC4702998 · DOI
  53. [57]Chung HY, Morita E, von Schwedler U, Müller B, Kräusslich HG, Sundquist WI. NEDD4L Overexpression Rescues the Release and Infectivity of Human Immunodeficiency Virus Type 1 Constructs Lacking PTAP and YPXL Late Domains. J Virol. 2008; 82: 4884– 4897. 10.1128/JVI.02667-07 18321968 PMC2346761 · DOI
  54. [58]Mercenne G, Alam SL, Arii J, Lalonde MS, Sundquist WI. Angiomotin functions in HIV-1 assembly and budding. Elife. 2015; 4: e03778. PMC4337731 25633977
  55. [59]Sette P, Jadwin JA, Dussupt V, Bello N, Bouamr F. The ESCRT-associated protein Alix recruits the ubiquitin ligase Nedd4-1 to facilitate HIV-1 release through the LYPXnL L domain motif. J Virol. 2010; 84: 8181– 8192. 10.1128/JVI.00634-10 20519395 PMC2916511 · DOI
  56. [60]Weiss ER, Popova E, Yamanaka H, Kim HC, Huibregtse JM, Göttlinger H. Rescue of HIV-1 Release by Targeting Widely Divergent NEDD4-Type Ubiquitin Ligases and Isolated Catalytic HECT Domains to Gag. PLoS Pathog. 2010; 6: e1001107 10.1371/journal.ppat.1001107 20862313 PMC2940739 · DOI
  57. [61]Ku P-I, Bendjennat M, Ballew J, Landesman MB, Saffarian S (2014) ALIX Is Recruited Temporarily into HIV-1 Budding Sites at the End of Gag Assembly. PLoS ONE 9: e96950 10.1371/journal.pone.0096950 24834918 PMC4023924 · DOI
  58. [62]Jouvenet N, Zhadina M, Bieniasz PD, Simon SM (2011) Dynamics of ESCRT protein recruitment during retroviral assembly. Nat Cell Biol 13: 394– 401. 10.1038/ncb2207 21394083 PMC3245320 · DOI
  59. [63]Carlton JG, Agromayor M, Martin-Serrano J. Differential requirements for ALIX and ESCRT-III in cytokinesis and HIV-1 release. Proc Natl Acad Sci U S A. 2008; 105: 10541– 10546. 10.1073/pnas.0802008105 18641129 PMC2492449 · DOI
  60. [64]Kräusslich HG. Human immunodeficiency virus proteinase dimer as component of the viral polyprotein prevents particle assembly and viral infectivity. Proc Natl Acad Sci U S A. 1991; 88: 3213– 3217. 2014242 PMC51416
  61. [65]Kaplan AH, Manchester M, Swanstrom R. The activity of the protease of human immunodeficiency virus type 1 is initiated at the membrane of infected cells before the release of viral proteins and is required for release to occur with maximum efficiency. J Virol. 1994; 68: 6782– 6786. 8084015 PMC237104
  62. [66]Ivanchenko S, Godinez WJ, Lampe M, Kräusslich HG, Eils R, Rohr K, Bräuchle C, Müller B, Lamb DC. Dynamics of HIV-1 Assembly and Release. PLoS Pathog. 2009; 5: e1000652 10.1371/journal.ppat.1000652 19893629 PMC2766258 · DOI
  63. [67]Pettit SC, Moody MD, Wehbie RS, Kaplan AH, Nantermet PV, Klein CA, Swanstrom R (1994) The p2 domain of human immunodeficiency virus type 1 Gag regulates sequential proteolytic processing and is required to produce fully infectious virions. Journal of Virology 68: 8017– 8027. 7966591 PMC237265
  64. [68]Chen BJ, Lamb RA. Mechanisms for enveloped virus budding: Can some viruses do without an ESCRT? Virology. 2008; 372: 221– 232. 18063004 PMC2751282
  65. [69]Rossman JS, Jing X, Leser GP, Lamb RA. Influenza Virus M2 Protein Mediates ESCRT-Independent Membrane Scission. Cell. 2010; 142: 902– 913. 10.1016/j.cell.2010.08.029 20850012 PMC3059587 · DOI
  66. [70]Swingler S, Gallay P, Camaur D, Song J, Abo A, Trono D. The Nef protein of human immunodeficiency virus type 1 enhances serine phosphorylation of the viral matrix. J Virol. 1997; 71: 4372– 4377. 9151826 PMC191654
  67. [71]Kofman A, Graf M, Bojak A, Deml L, Bieler K, Kharazova A, Wolf H, Wagner R. HIV-1 gag expression is quantitatively dependent on the ratio of native and optimized codons. Tsitologiia. 2003; 45: 86– 93. 12683241
  68. [72]Macia E, Ehrlich M, Massol R, Boucrot E, Brunner C, Kirchhausen T (2006) Dynasore, a Cell-Permeable Inhibitor of Dynamin. Developmental Cell 10: 839– 850. 16740485
  69. [73]Kirchhausen T, Macia E, Pelish HE (2008) Use of Dynasore, the Small Molecule Inhibitor of Dynamin, in the Regulation of Endocytosis Methods in Enzymology: Academic Press pp. 77– 93 PMC2796620 18413242

Cited by

Sorted by citations

Authors
Bendjennat, M., & Saffarian, S.
Affiliations
University of Utah (US)
Corresponding author
Saffarian, Saveez
ORCID
Venue
PLOS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2016-06-09
Volume
12
Issue
6
Pages
e1005657
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1005657
PMC
PMC4900648
OpenAlex
W2414000364
Cited by
45
References
4
Citations by year
2026: 3 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 9 · 2019: 5 · 2018: 4 · 2017: 1 · 2016: 1
FWCI
2.54
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
National Institute of Allergy and Infectious Diseases (R21 AI114432-02)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Keywords
HIV budding, ESCRT, Gag, Alix, TSG101, Gag-Pol, virion maturation, HIV-1
MeSH terms
Cell Line, Humans, Monte Carlo Method, Peptide Hydrolases, HIV-1, HIV Infections, gag Gene Products, Human Immunodeficiency Virus, Endosomal Sorting Complexes Required for Transport, Virus Release

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review