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Ex Vivo HIV Infection Model of Cervico-Vaginal and Rectal Tissue

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HIV Reservoirs

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2407))

Abstract

Globally, the most frequent route of HIV transmission is through sexual intercourse. In women, sexual transmission of HIV involves cervical, vaginal, endometrial, and rectal mucosal exposure to the virus. Here we describe technical protocols for ex vivo cervical, vaginal, and rectal tissue infection models and cultures that can be used to assess tissue susceptibility to infection under different conditions as well as the potential antiviral efficacy of a treatment for HIV prevention or cure.

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References

  1. Cohen MS (2007) Preventing sexual transmission of HIV. Clin Infect Dis 45(Supplement_4):S287–S292. https://doi.org/10.1086/522552

    Article  PubMed  Google Scholar 

  2. Hladik F, Hope TJ (2009) HIV infection of the genital mucosa in women. Curr HIV/AIDS Rep 6(1):20–28

    Article  PubMed  Google Scholar 

  3. Hladik F, McElrath MJ (2008) Setting the stage: host invasion by HIV. Nat Rev Immunol 8(6):447–457. https://doi.org/10.1038/nri2302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. García-Lerma JG, Heneine W (2012) Animal models of antiretroviral prophylaxis for HIV prevention. Curr Opin HIV AIDS 7(6):505–513. https://doi.org/10.1097/COH.0b013e328358e484

    Article  PubMed  Google Scholar 

  5. Pope M, Haase AT (2003) Transmission, acute HIV-1 infection and the quest for strategies to prevent infection. Nat Med 9(7):847–852. https://doi.org/10.1038/nm0703-847

    Article  CAS  PubMed  Google Scholar 

  6. Haase AT (2011) Early events in sexual transmission of HIV and SIV and opportunities for interventions. Annu Rev Med 62:127–139. https://doi.org/10.1146/annurev-med-080709-124959

    Article  CAS  PubMed  Google Scholar 

  7. Gonzalez SM, Aguilar-Jimenez W, Su RC, Rugeles MT (2019) Mucosa: key interactions determining sexual transmission of the HIV infection. Front Immunol 10:144. https://doi.org/10.3389/fimmu.2019.00144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Stieh DJ, Matias E, Xu H, Fought AJ, Blanchard JL, Marx PA, Veazey RS, Hope TJ (2016) Th17 cells are preferentially infected very early after vaginal transmission of SIV in macaques. Cell Host Microbe 19(4):529–540. https://doi.org/10.1016/j.chom.2016.03.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dezzutti CS, Uranker K, Bunge KE, Richardson-Harman N, Macio I, Hillier SL (2013) HIV-1 infection of female genital tract tissue for use in prevention studies. J Acquir Immune Defic Syndr 63(5):548–554. https://doi.org/10.1097/QAI.0b013e318291f331

    Article  PubMed  PubMed Central  Google Scholar 

  10. Fletcher PS, Elliott J, Grivel JC, Margolis L, Anton P, McGowan I, Shattock RJ (2006) Ex vivo culture of human colorectal tissue for the evaluation of candidate microbicides. AIDS 20(9):1237–1245. https://doi.org/10.1097/01.aids.0000232230.96134.80

    Article  PubMed  Google Scholar 

  11. Hladik F, Sakchalathorn P, Ballweber L, Lentz G, Fialkow M, Eschenbach D, McElrath MJ (2007) Initial events in establishing vaginal entry and infection by human immunodeficiency virus type-1. Immunity 26(2):257–270. https://doi.org/10.1016/j.immuni.2007.01.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Palacio J, Souberbielle BE, Shattock RJ, Robinson G, Manyonda I, Griffin GE (1994) In vitro HIV1 infection of human cervical tissue. Res Virol 145(3–4):155–161. https://doi.org/10.1016/s0923-2516(07)80017-3

    Article  CAS  PubMed  Google Scholar 

  13. Ouattara LA, Anderson SM, Doncel GF (2018) Seminal exosomes and HIV-1 transmission. Andrologia 50(11):e13220. https://doi.org/10.1111/and.13220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hladik F, Doncel GF (2010) Preventing mucosal HIV transmission with topical microbicides: challenges and opportunities. Antivir Res 88(Suppl 1):S3–S9. https://doi.org/10.1016/j.antiviral.2010.09.011

    Article  CAS  PubMed  Google Scholar 

  15. Thurman AR, Yousefieh N, Chandra N, Kimble T, Asin S, Rollenhagen C, Anderson SM, Herold BC, Freiermuth JL, Starkman BS, Mesquita PMM, Richardson-Harman N, Cunningham T, Hillier S, Rabe L, Schwartz JL, Doncel GF (2017) Comparison of mucosal markers of human immunodeficiency virus susceptibility in healthy premenopausal versus postmenopausal women. AIDS Res Hum Retrovir 33(8):807–819. https://doi.org/10.1089/AID.2016.0320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Thurman A, Chandra N, Schwartz JL, Brache V, Chen BA, Asin S, Rollenhagen C, Herold BC, Fichorova RN, Hillier SL, Weiner DH, Mauck C, Doncel GF (2019) The effect of hormonal contraception on cervicovaginal mucosal end points associated with HIV acquisition. AIDS Res Hum Retroviruses 35(9):853–864. https://doi.org/10.1089/aid.2018.0298

    Article  CAS  PubMed  Google Scholar 

  17. Zalenskaya IA, Chandra N, Yousefieh N, Fang X, Adedipe OE, Jackson SS, Anderson SM, Mauck CK, Schwartz JL, Thurman AR, Doncel GF (2018) Use of contraceptive depot medroxyprogesterone acetate is associated with impaired cervicovaginal mucosal integrity. J Clin Invest 128(10):4622–4638. https://doi.org/10.1172/JCI120583

    Article  PubMed  PubMed Central  Google Scholar 

  18. Abner SR, Guenthner PC, Guarner J, Hancock KA, Cummins JE Jr, Fink A, Gilmore GT, Staley C, Ward A, Ali O, Binderow S, Cohen S, Grohskopf LA, Paxton L, Hart CE, Dezzutti CS (2005) A human colorectal explant culture to evaluate topical microbicides for the prevention of HIV infection. J Infect Dis 192(9):1545–1556. https://doi.org/10.1086/462424

    Article  CAS  PubMed  Google Scholar 

  19. Greenhead P, Hayes P, Watts PS, Laing KG, Griffin GE, Shattock RJ (2000) Parameters of human immunodeficiency virus infection of human cervical tissue and inhibition by vaginal virucides. J Virol 74(12):5577–5586. https://doi.org/10.1128/jvi.74.12.5577-5586.2000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Richardson-Harman N, Mauck C, McGowan I, Anton P (2012) Dose-response relationship between tissue concentrations of UC781 and explant infectibility with HIV type 1 in the RMP-01 rectal safety study. AIDS Res Hum Retrovir 28(11):1422–1433. https://doi.org/10.1089/AID.2012.0073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Dezzutti CS, Hladik F (2013) Use of human mucosal tissue to study HIV-1 pathogenesis and evaluate HIV-1 prevention modalities. Curr HIV/AIDS Rep 10(1):12–20. https://doi.org/10.1007/s11904-012-0148-2

    Article  PubMed  PubMed Central  Google Scholar 

  22. Patterson BK, Landay A, Siegel JN, Flener Z, Pessis D, Chaviano A, Bailey RC (2002) Susceptibility to human immunodeficiency virus-1 infection of human foreskin and cervical tissue grown in explant culture. Am J Pathol 161(3):867–873. https://doi.org/10.1016/S0002-9440(10)64247-2

    Article  PubMed  PubMed Central  Google Scholar 

  23. Thurman AR, Schwartz JL, Brache V, Clark MR, McCormick T, Chandra N, Marzinke MA, Stanczyk FZ, Dezzutti CS, Hillier SL, Herold BC, Fichorova R, Asin SN, Rollenhagen C, Weiner D, Kiser P, Doncel GF (2018) Randomized, placebo controlled phase I trial of safety, pharmacokinetics, pharmacodynamics and acceptability of tenofovir and tenofovir plus levonorgestrel vaginal rings in women. PLoS One 13(6):e0199778. https://doi.org/10.1371/journal.pone.0199778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Anton PA, Cranston RD, Kashuba A, Hendrix CW, Bumpus NN, Richardson-Harman N, Elliott J, Janocko L, Khanukhova E, Dennis R, Cumberland WG, Ju C, Carballo-Dieguez A, Mauck C, McGowan I (2012) RMP-02/MTN-006: a phase 1 rectal safety, acceptability, pharmacokinetic, and pharmacodynamic study of tenofovir 1% gel compared with oral tenofovir disoproxil fumarate. AIDS Res Hum Retrovir 28(11):1412–1421. https://doi.org/10.1089/AID.2012.0262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Anton PA, Saunders T, Elliott J, Khanukhova E, Dennis R, Adler A, Cortina G, Tanner K, Boscardin J, Cumberland WG, Zhou Y, Ventuneac A, Carballo-Dieguez A, Rabe L, McCormick T, Gabelnick H, Mauck C, McGowan I (2011) First phase 1 double-blind, placebo-controlled, randomized rectal microbicide trial using UC781 gel with a novel index of ex vivo efficacy. PLoS One 6(9):e23243. https://doi.org/10.1371/journal.pone.0023243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Richardson-Harman N, Parody R, Anton P, McGowan I, Doncel G, Thurman AR, Herrera C, Kordy K, Fox J, Tanner K, Swartz G, Dezzutti CS (2017) Analytical advances in the ex vivo challenge efficacy assay. AIDS Res Hum Retrovir 33(4):395–403. https://doi.org/10.1089/AID.2016.0073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. von Sydow M, Gaines H, Sonnerborg A, Forsgren M, Pehrson PO, Strannegard O (1988) Antigen detection in primary HIV infection. Br Med J (Clin Res Ed) 296(6617):238–240. https://doi.org/10.1136/bmj.296.6617.238

    Article  Google Scholar 

  28. Richardson-Harman N, Lackman-Smith C, Fletcher PS, Anton PA, Bremer JW, Dezzutti CS, Elliott J, Grivel JC, Guenthner P, Gupta P, Jones M, Lurain NS, Margolis LB, Mohan S, Ratner D, Reichelderfer P, Roberts P, Shattock RJ, Cummins JE Jr (2009) Multisite comparison of anti-human immunodeficiency virus microbicide activity in explant assays using a novel endpoint analysis. J Clin Microbiol 47(11):3530–3539. https://doi.org/10.1128/JCM.00673-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Glushakova S, Grivel JC, Suryanarayana K, Meylan P, Lifson JD, Desrosiers R, Margolis L (1999) Nef enhances human immunodeficiency virus replication and responsiveness to interleukin-2 in human lymphoid tissue ex vivo. J Virol 73(5):3968–3974. https://doi.org/10.1128/JVI.73.5.3968-3974.1999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Natarajan V, Lempicki RA, Sereti I, Badralmaa Y, Adelsberger JW, Metcalf JA, Prieto DA, Stevens R, Baseler MW, Kovacs JA, Lane HC (2002) Increased peripheral expansion of naive CD4+ T cells in vivo after IL-2 treatment of patients with HIV infection. Proc Natl Acad Sci U S A 99(16):10712–10717. https://doi.org/10.1073/pnas.162352399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. CONRAD, Eastern Virginia Medical School, Norfolk, VA, USA

    Louise A. Ouattara, Nikolas C. Vann & Gustavo F. Doncel

Authors
  1. Louise A. Ouattara
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  2. Nikolas C. Vann
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  3. Gustavo F. Doncel
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Corresponding author

Correspondence to Louise A. Ouattara .

Editor information

Editors and Affiliations

  1. School of Medicine and Human Immuno-Virology (H.I.V.) Group, San Raffaele University and Scientific Institute, Milano, Italy

    Guido Poli

  2. Viral Pathogenesis and Biosafety Group, San Raffaele Scientific Institute, Milano, Italy

    Elisa Vicenzi

  3. Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Fabio Romerio

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Ouattara, L.A., Vann, N.C., Doncel, G.F. (2022). Ex Vivo HIV Infection Model of Cervico-Vaginal and Rectal Tissue. In: Poli, G., Vicenzi, E., Romerio, F. (eds) HIV Reservoirs. Methods in Molecular Biology, vol 2407. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1871-4_12

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  • DOI: https://doi.org/10.1007/978-1-0716-1871-4_12

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1870-7

  • Online ISBN: 978-1-0716-1871-4

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