دورية أكاديمية
أعرض في EDS

Humanized Mouse Model of HIV-1 Latency with Enrichment of Latent Virus in PD-1 + and TIGIT + CD4 T Cells.

التفاصيل البيبلوغرافية
العنوان: Humanized Mouse Model of HIV-1 Latency with Enrichment of Latent Virus in PD-1 + and TIGIT + CD4 T Cells.
المؤلفون: Llewellyn GN; Department of Molecular Microbiology and Immunology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA., Seclén E; Department of Molecular Microbiology and Immunology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA., Wietgrefe S; Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA., Liu S; School of Pharmacy, University of Southern California, Los Angeles, California, USA., Chateau M; Department of Molecular Microbiology and Immunology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA., Pei H; School of Pharmacy, University of Southern California, Los Angeles, California, USA., Perkey K; Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA., Marsden MD; Department of Medicine, University of California Los Angeles, Los Angeles, California, USA.; Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, California, USA., Hinkley SJ; Sangamo Therapeutics, Inc., Richmond, California, USA., Paschon DE; Sangamo Therapeutics, Inc., Richmond, California, USA., Holmes MC; Sangamo Therapeutics, Inc., Richmond, California, USA., Zack JA; Department of Medicine, University of California Los Angeles, Los Angeles, California, USA.; Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, California, USA., Louie SG; School of Pharmacy, University of Southern California, Los Angeles, California, USA., Haase AT; Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA., Cannon PM; Department of Molecular Microbiology and Immunology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA pcannon@usc.edu.
المصدر: Journal of virology [J Virol] 2019 May 01; Vol. 93 (10). Date of Electronic Publication: 2019 May 01 (Print Publication: 2019).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE
أسماء مطبوعة: Publication: Washington Dc : American Society For Microbiology
Original Publication: Baltimore, American Society for Microbiology.
مواضيع طبية MeSH: HIV-1/*immunology , Virus Latency/*immunology , Virus Latency/*physiology, Animals ; Anti-Retroviral Agents/pharmacology ; CD4-Positive T-Lymphocytes/metabolism ; CD4-Positive T-Lymphocytes/virology ; Disease Models, Animal ; HIV Infections/virology ; HIV Seropositivity/drug therapy ; HIV-1/pathogenicity ; Humans ; Mice ; Programmed Cell Death 1 Receptor/immunology ; Receptors, Immunologic/immunology ; Transcription Activator-Like Effector Nucleases/immunology ; Virus Activation ; Virus Replication
مستخلص: Combination anti-retroviral drug therapy (ART) potently suppresses HIV-1 replication but does not result in virus eradication or a cure. A major contributing factor is the long-term persistence of a reservoir of latently infected cells. To study this reservoir, we established a humanized mouse model of HIV-1 infection and ART suppression based on an oral ART regimen. Similar to humans, HIV-1 levels in the blood of ART-treated animals were frequently suppressed below the limits of detection. However, the limited timeframe of the mouse model and the small volume of available samples makes it a challenging model with which to achieve full viral suppression and to investigate the latent reservoir. We therefore used an ex vivo latency reactivation assay that allows a semiquantitative measure of the latent reservoir that establishes in individual animals, regardless of whether they are treated with ART. Using this assay, we found that latently infected human CD4 T cells can be readily detected in mouse lymphoid tissues and that latent HIV-1 was enriched in populations expressing markers of T cell exhaustion, PD-1 and TIGIT. In addition, we were able to use the ex vivo latency reactivation assay to demonstrate that HIV-specific TALENs can reduce the fraction of reactivatable virus in the latently infected cell population that establishes in vivo , supporting the use of targeted nuclease-based approaches for an HIV-1 cure. IMPORTANCE HIV-1 can establish latent infections that are not cleared by current antiretroviral drugs or the body's immune responses and therefore represent a major barrier to curing HIV-infected individuals. However, the lack of expression of viral antigens on latently infected cells makes them difficult to identify or study. Here, we describe a humanized mouse model that can be used to detect latent but reactivatable HIV-1 in both untreated mice and those on ART and therefore provides a simple system with which to study the latent HIV-1 reservoir and the impact of interventions aimed at reducing it.
(Copyright © 2019 American Society for Microbiology.)
References: J Infect Dis. 2001 Feb 15;183(4):555-62. (PMID: 11170980)
PLoS Pathog. 2015 Sep 17;11(9):e1005142. (PMID: 26379282)
PLoS Pathog. 2016 Apr 27;12(4):e1005535. (PMID: 27119536)
Retrovirology. 2013 Oct 24;10:121. (PMID: 24156277)
J Virol. 2013 Aug;87(16):9148-58. (PMID: 23760244)
PLoS Pathog. 2015 Jun 11;11(6):e1004955. (PMID: 26067822)
J Mol Biol. 2011 Jul 29;410(5):896-916. (PMID: 21763495)
Science. 1997 Nov 14;278(5341):1291-5. (PMID: 9360926)
Viruses. 2019 Jan 27;11(2):. (PMID: 30691203)
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13193-7. (PMID: 9371822)
AIDS Rev. 2011 Jul-Sep;13(3):135-48. (PMID: 21799532)
J Biol Chem. 2016 May 6;291(19):10332-46. (PMID: 26957545)
J Virus Erad. 2017 Jan 1;3(1):61-65. (PMID: 28275460)
Immunity. 2012 Mar 23;36(3):491-501. (PMID: 22406268)
J Virol. 2014 Dec;88(24):14070-7. (PMID: 25253353)
PLoS Med. 2008 Jan 15;5(1):e16. (PMID: 18198941)
PLoS Biol. 2011 Nov;9(11):e1001206. (PMID: 22140357)
PLoS One. 2011 Apr 05;6(4):e18270. (PMID: 21483687)
Cell Rep. 2017 Oct 17;21(3):813-822. (PMID: 29045846)
Sci Rep. 2016 Mar 04;6:22555. (PMID: 26939770)
Nat Med. 2016 Jul;22(7):754-61. (PMID: 27239760)
J Infect Dis. 2007 May 15;195(10):1426-36. (PMID: 17436222)
Methods Mol Biol. 2010;649:247-56. (PMID: 20680839)
PLoS Pathog. 2013;9(5):e1003338. (PMID: 23658523)
Sci Transl Med. 2018 Apr 18;10(437):. (PMID: 29669853)
Nature. 2017 Mar 23;543(7646):564-567. (PMID: 28297712)
Nat Biotechnol. 2011 Feb;29(2):143-8. (PMID: 21179091)
Proc Natl Acad Sci U S A. 2014 Aug 5;111(31):11461-6. (PMID: 25049410)
Antiviral Res. 2016 Feb;126:90-8. (PMID: 26718067)
Methods Mol Biol. 2016;1354:239-53. (PMID: 26714716)
Nat Biotechnol. 2015 Dec;33(12):1256-1263. (PMID: 26551060)
Blood. 2004 May 15;103(10):3964-9. (PMID: 14739221)
Mol Ther Nucleic Acids. 2018 Sep 7;12:275-282. (PMID: 30195766)
Nat Med. 2016 Aug;22(8):839-50. (PMID: 27400264)
J Virol. 1999 Mar;73(3):2343-9. (PMID: 9971817)
Antimicrob Agents Chemother. 2003 Oct;47(10):3123-9. (PMID: 14506019)
EMBO J. 2003 Apr 15;22(8):1868-77. (PMID: 12682019)
PLoS Pathog. 2013;9(9):e1003587. (PMID: 24086129)
J Virol. 2012 Jan;86(1):630-4. (PMID: 22013053)
AIDS. 2008 Aug 20;22(13):1583-8. (PMID: 18670217)
Nat Biotechnol. 2016 Apr;34(4):401-9. (PMID: 26900663)
Proc Natl Acad Sci U S A. 2018 Aug 14;115(33):E7795-E7804. (PMID: 30061382)
Proc Natl Acad Sci U S A. 1993 May 15;90(10):4674-8. (PMID: 7685108)
Virology. 2017 Jul;507:135-139. (PMID: 28432928)
Cell Rep. 2016 Apr 19;15(3):481-489. (PMID: 27068471)
Nat Commun. 2015 Mar 10;6:6413. (PMID: 25752527)
Nat Med. 2009 Aug;15(8):893-900. (PMID: 19543283)
Front Immunol. 2018 Feb 05;9:144. (PMID: 29459864)
PLoS Pathog. 2016 Jul 14;12(7):e1005761. (PMID: 27415008)
Nat Med. 2003 Jun;9(6):727-8. (PMID: 12754504)
Science. 2007 Jun 29;316(5833):1912-5. (PMID: 17600219)
Sci Rep. 2018 Feb 8;8(1):2639. (PMID: 29422601)
Nucleic Acids Res. 2013 Sep;41(16):7771-82. (PMID: 23804764)
J Exp Med. 2013 Jan 14;210(1):143-56. (PMID: 23254284)
Science. 1997 Nov 14;278(5341):1295-300. (PMID: 9360927)
Transcription. 2012 Jul-Aug;3(4):171-6. (PMID: 22771990)
EBioMedicine. 2015 Jun 27;2(8):874-83. (PMID: 26425694)
Nat Med. 2017 Nov;23(11):1271-1276. (PMID: 28967921)
Nat Biotechnol. 2010 Aug;28(8):839-47. (PMID: 20601939)
Blood. 2008 Apr 15;111(8):4293-6. (PMID: 18270327)
J Virol. 1994 Aug;68(8):4768-75. (PMID: 8035478)
AIDS. 2017 Jan 2;31(1):35-48. (PMID: 27835617)
Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2307-12. (PMID: 24469825)
J Virol. 2012 Jan;86(1):114-20. (PMID: 22013038)
Cell. 2013 Oct 24;155(3):540-51. (PMID: 24243014)
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16725-30. (PMID: 18936487)
PLoS Pathog. 2017 Sep 21;13(9):e1006575. (PMID: 28934369)
Nat Biotechnol. 2011 Feb;29(2):135-6. (PMID: 21301438)
Nature. 2015 Jan 15;517(7534):381-5. (PMID: 25561180)
Sci Rep. 2013;3:2510. (PMID: 23974631)
PLoS Pathog. 2013;9(5):e1003398. (PMID: 23737751)
Nat Med. 2006 Nov;12(11):1316-22. (PMID: 17057712)
Curr HIV Res. 2016;14(5):431-441. (PMID: 27009094)
mBio. 2017 Jul 11;8(4):. (PMID: 28698276)
Cell. 2014 Aug 28;158(5):989-999. (PMID: 25131989)
Blood. 2006 Jul 15;108(2):487-92. (PMID: 16410443)
Nature. 2012 Jul 25;487(7408):482-5. (PMID: 22837004)
AIDS. 2018 Jan 2;32(1):1-10. (PMID: 29112072)
AIDS Res Hum Retroviruses. 2009 Feb;25(2):207-12. (PMID: 19239360)
J Virol. 2018 Mar 14;92(7):. (PMID: 29343582)
Virology. 2015 Nov;485:1-15. (PMID: 26184775)
J Infect Dis. 2015 Nov 1;212(9):1387-96. (PMID: 25883388)
Nat Chem. 2012 Sep;4(9):705-10. (PMID: 22914190)
PLoS One. 2012;7(6):e38853. (PMID: 22719966)
Nature. 2016 Feb 4;530(7588):51-56. (PMID: 26814962)
PLoS Pathog. 2014 Jan;10(1):e1003872. (PMID: 24415939)
mBio. 2017 Feb 28;8(1):. (PMID: 28246360)
J Virol. 2009 Jul;83(14):7305-21. (PMID: 19420076)
Nat Commun. 2018 Nov 16;9(1):4811. (PMID: 30446650)
J Clin Virol. 2008 Aug;42(4):399-404. (PMID: 18455956)
J Virol. 2012 Jan;86(1):339-47. (PMID: 22072769)
Methods Mol Biol. 2014;1087:261-70. (PMID: 24158829)
J Infect Dis. 2013 Jun 1;207(11):1694-702. (PMID: 23460751)
Trends Microbiol. 2015 Apr;23(4):192-203. (PMID: 25747663)
Ann Intern Med. 2014 Sep 2;161(5):319-27. (PMID: 25047577)
PLoS Pathog. 2013 Feb;9(2):e1003174. (PMID: 23459007)
Science. 1996 Nov 8;274(5289):985-9. (PMID: 8875941)
J Virol. 1998 Sep;72(9):6988-96. (PMID: 9696790)
Retrovirology. 2015 Feb 27;12:22. (PMID: 25808449)
JAMA. 2014 Jul 23-30;312(4):410-25. (PMID: 25038359)
PLoS One. 2015 Mar 17;10(3):e0120047. (PMID: 25781496)
Mol Cell Biol. 2014 Jun;34(11):1911-28. (PMID: 24636995)
Mol Ther. 2016 Mar;24(3):522-6. (PMID: 26796669)
J Infect Dis. 2011 Jul 1;204(1):135-8. (PMID: 21628667)
J Virol Methods. 2006 Apr;133(1):41-7. (PMID: 16307801)
PLoS Pathog. 2018 Feb 22;14(2):e1006856. (PMID: 29470552)
Mol Ther. 2017 May 3;25(5):1168-1186. (PMID: 28366764)
Science. 2009 Mar 6;323(5919):1304-7. (PMID: 19265012)
PLoS One. 2015 May 06;10(5):e0125652. (PMID: 25946221)
معلومات مُعتمدة: R01 MH113457 United States MH NIMH NIH HHS; R21 AI110149 United States AI NIAID NIH HHS; R33 AI110149 United States AI NIAID NIH HHS; U19 HL129902 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: HIV-1; PD-1; TALEN; TIGIT; humanized mice; latency
المشرفين على المادة: 0 (Anti-Retroviral Agents)
0 (Programmed Cell Death 1 Receptor)
0 (Receptors, Immunologic)
0 (TIGIT protein, human)
EC 3.1.- (Transcription Activator-Like Effector Nucleases)
تواريخ الأحداث: Date Created: 20190308 Date Completed: 20200302 Latest Revision: 20201215
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6498059
DOI: 10.1128/JVI.02086-18
PMID: 30842333
قاعدة البيانات: MEDLINE
الوصف
تدمد:1098-5514
DOI:10.1128/JVI.02086-18