Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection

1. Kuller LH, Tracy R, Belloso W, Wit S De, Drummond F, Lane HC, et al. Inflammatory and Coagulation Biomarkers and Mortality in Patients with HIV Infection. PLoS Med. 2008;5: 1496–1508. doi: 10.1371/journal.pmed.0050203

2. Deeks SG. HIV Infection, Inflammation, and Aging. Annu Rev Med. 2011;62: 141–055. doi: 10.1146/annurev-med-042909-093756 21090961

3. Deeks SG, Tracy R, Douek DC. Systemic effects of inflammation on health during chronic HIV infection. Immunity. 2013;39: 633–45. doi: 10.1016/j.immuni.2013.10.001 24138880

4. Hunt PW, Brenchley J, Sinclair E, Mccune JM, Roland M, Page-shafer K, et al. Relationship between T Cell Activation and CD4+ T Cell Count in HIV-Seropositive Individuals with Undetectable Plasma HIV RNA Levels in the Absence of Therapy. J Infect Dis. 2008;197: 126–133. doi: 10.1086/524143 18171295

5. Noel N, Boufassa F, Lécuroux C, Saez-Cirion A, Bourgeois C, Dunyach-Remy C, et al. Elevated IP10 levels are associated with immune activation and low CD4+ T-cell counts in HIV controller patients. AIDS. 2014;28: 467–76. doi: 10.1097/QAD.0000000000000174 24378753

6. Eisele E, Siliciano RF. Redefining the viral reservoirs that prevent HIV-1 eradication. Immunity. 2012;37: 377–88. doi: 10.1016/j.immuni.2012.08.010 22999944

7. Lambert-Niclot S, Tubiana R, Beaudoux C, Lefebvre G, Caby F, Bonmarchand M, et al. Detection of HIV-1 RNA in seminal plasma samples from treated patients with undetectable HIV-1 RNA in blood plasma on a 2002–2011 survey. AIDS. 2012;26: 971–5. doi: 10.1097/QAD.0b013e328352ae09 22382146

8. Zink MC, Brice AK, Kelly KM, Queen SE, Gama L, Li M, et al. Simian immunodeficiency virus-infected macaques treated with highly active antiretroviral therapy have reduced central nervous system viral replication and inflammation but persistence of viral DNA. J Infect Dis. 2010;202: 161–70. doi: 10.1086/653213 20497048

9. Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12: 1365–1371. 17115046

10. Appay V, Sauce D. Immune activation and inflammation in HIV-1 infection : causes and consequences. J Pathol. 2008;214: 231–241. doi: 10.1002/path.2276 18161758

11. Paiardini M, Müller-Trutwin M. HIV-associated chronic immune activation. Immunol Rev. 2013;254: 78–101. doi: 10.1111/imr.12079 23772616

12. Costiniuk CT, Angel JB. Human immunodeficiency virus and the gastrointestinal immune system: does highly active antiretroviral therapy restore gut immunity? Mucosal Immunol. 2012;5: 596–604. doi: 10.1038/mi.2012.82 22929559

13. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89: 2548–2556. 15181022

14. Madani R, Karastergiou K, Ogston NC, Miheisi N, Bhome R, Haloob N, et al. RANTES release by human adipose tissue in vivo and evidence for depot-specific differences. Am J Physiol Endocrinol Metab. 2009;296: E1262–8. doi: 10.1152/ajpendo.90511.2008 19240255

15. Bruun JM, Lihn AS, Pedersen SB, Richelsen B. Monocyte Chemoattractant Protein-1 Release Is Higher in Visceral than Subcutaneous Human Adipose Tissue (AT): Implication of Macrophages Resident in the AT. 2005;90: 2282–2289. doi: 10.1210/jc.2004-1696 15671098

16. Maury E, Ehala-Aleksejev K, Guiot Y, Detry R, Vandenhooft A, Brichard SM. Adipokines oversecreted by omental adipose tissue in human obesity. Am J Physiol Endocrinol Metab. 2007;293: E656–65. 17578888

17. Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab. 1997;82: 4196–200. doi: 10.1210/jcem.82.12.4450 9398739

18. Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab. 1998;83: 847–50. doi: 10.1210/jcem.83.3.4660 9506738

19. Stofkova A. Leptin and adiponectin: from energy and metabolic dysbalance to inflammation and autoimmunity. Endocr Regul. 2009;43: 157–68. 19908934

20. Procaccini C, Lourenco E V, Matarese G, La Cava A. Leptin signaling: A key pathway in immune responses. Curr Signal Transduct Ther. 2009;4: 22–30. doi: 10.2174/157436209787048711 19774101

21. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Publ Gr. Nature Publishing Group; 2011;11: 85–97. doi: 10.1038/nri2921

22. Hotamisligil GS. Inflammation and metabolic disorders. 2006;444. doi: 10.1038/nature05485 17167474

23. Mathis D, Shoelson SE. Immunometabolism: an emerging frontier. Nat Rev Immunol. 2011;11: 81. doi: 10.1038/nri2922 21469396

24. Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. 2007;117. doi: 10.1172/JCI29881 both 17200717

25. Hruskova Z, Biswas SK. Previews A New “‘ Immunological ‘” Role for Adipocytes in Obesity. CMET. Elsevier; 2013;17: 315–317. doi: 10.1016/j.cmet.2013.02.015

26. Weisberg SP, Mccann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112: 1796–1808. doi: 10.1172/JCI200319246 Introduction 14679176

27. Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009;15: 914–920. doi: 10.1038/nm.1964 19633658

28. Duffaut C, Zakaroff-Girard A, Bourlier V, Decaunes P, Maumus M, Chiotasso P, et al. Interplay between human adipocytes and T lymphocytes in obesity: CCL20 as an adipochemokine and T lymphocytes as lipogenic modulators. Arter Thromb Vasc Biol. 2009;29: 1608–1614.

29. Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. Nature Publishing Group; 2009;15: 1–11. doi: 10.1038/nm.2002

30. Deng T, Lyon CJ, Minze LJ, Lin J, Zou J, Liu JZ, et al. Article Class II Major Histocompatibility Complex Plays an Essential Role in Obesity-Induced Adipose Inflammation. Cell Metab. Elsevier Inc.; 2013;17: 411–422. doi: 10.1016/j.cmet.2013.02.009 23473035

31. Guilherme A, Virbasius J V, Puri V, Czech MP. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol. 2008;9: 367–77. doi: 10.1038/nrm2391 18401346

32. Suganami T, Nishida J, Ogawa Y. A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol. 2005;25: 2062–8. doi: 10.1161/01.ATV.0000183883.72263.13 16123319

33. Giralt M, Domingo P, Guallar JP, Rodriguez de la Concepción ML, Alegre M, Domingo JC, et al. HIV-1 infection alters gene expression in adipose tissue, which contributes to HIV- 1/HAART-associated lipodystrophy. Antivir Ther. 2006;11: 729–40. 17310817

34. Giralt M, Domingo P, Villarroya F. Adipose tissue biology and HIV-infection. Best Pract Res Clin Endocrinol Metab. Elsevier Ltd; 2011;25: 487–99. doi: 10.1016/j.beem.2010.12.001 21663842

35. Capel E, Auclair M, Caron-Debarle M, Capeau J. Effects of ritonavir-boosted darunavir, atazanavir and lopinavir on adipose functions and insulin sensitivity in murine and human adipocytes. Antivir Ther. 2012;17: 549–56. doi: 10.3851/IMP1988 22293506

36. Caron-Debarle M, Lagathu C, Boccara F, Vigouroux C, Capeau J. HIV-associated lipodystrophy: from fat injury to premature aging. Trends Mol Med. Elsevier Ltd; 2010;16: 218–29. doi: 10.1016/j.molmed.2010.03.002 20400373

37. Díaz-Delfín J, Domingo P, Wabitsch M, Giralt M, Villarroya F. HIV-1 Tat protein impairs adipogenesis and induces the expression and secretion of proinflammatory cytokines in human SGBS adipocytes. Antivir Ther. 2012;17: 529–40. doi: 10.3851/IMP2021 22301094

38. Díaz-Delfín J, Domingo P, Mateo MG, Gutierrez MDM, Domingo JC, Giralt M, et al. Effects of rilpivirine on human adipocyte differentiation, gene expression, and release of adipokines and cytokines. Antimicrob Agents Chemother. 2012;56: 3369–75. doi: 10.1128/AAC.00104-12 22430974

39. Lindegaard B, Hansen A-BE, Pilegaard H, Keller P, Gerstoft J, Pedersen BK. Adipose tissue expression of IL-18 and HIV-associated lipodystrophy. AIDS. 2004;18: 1956–8. 15353983

40. Jan V, Cervera P, Maachi M, Baudrimont M, Kim M, Vidal H, et al. Altered fat differentiation and adipocytokine expression are inter-related and linked to morphological changes and insulin resistance in HIV-1-infected lipodystrophic patients. Antivir Ther. 2004;9: 555–64. 15456087

41. Johnson JA, Albu JB, Engelson ES, Fried SK, Inada Y, Ionescu G, et al. Increased systemic and adipose tissue cytokines in patients with HIV-associated lipodystrophy. Am J Physiol Endocrinol Metab. 2004;286: E261–71. doi: 10.1152/ajpendo.00056.2003 14532165

42. Gallego-Escuredo JM, Villarroya J, Domingo P, Targarona EM, Alegre M, Domingo JC, et al. Differentially altered molecular signature of visceral adipose tissue in HIV-1-associated lipodystrophy. J Acquir Immune Defic Syndr. 2013;64: 142–8. doi: 10.1097/QAI.0b013e31829bdb67 23714743

43. Shikuma CM, Gangcuangco LMA, Killebrew DA, Libutti DE, Chow DC, Nakamoto BK, et al. The role of HIV and monocytes/macrophages in adipose tissue biology. J Acquir Immune Defic Syndr. 2014;65: 151–9. doi: 10.1097/01.qai.0000435599.27727.6c 24091690

44. Dupin N, Buffet M, Marcelin A-G, Lamotte C, Gorin I, Ait-Arkoub Z, et al. HIV and antiretroviral drug distribution in plasma and fat tissue of HIV-infected patients with lipodystrophy. AIDS. 2002;16: 2419–24. 12461415

45. Hazan U, Romero IA, Cancello R, Valente S, Perrin V, Mariot V, et al. Human adipose cells express CD4, CXCR4, and CCR5 [corrected] receptors: a new target cell type for the immunodeficiency virus-1? FASEB J. 2002;16: 1254–6. doi: 10.1096/fj.01-0947fje 12153994

46. Munier S, Borjabad A, Lemaire M, Mariot V, Hazan U. In vitro infection of human primary adipose cells with HIV-1: a reassessment. AIDS. 2003;17: 2537–9. doi: 10.1097/01.aids.0000096866.36052.84 14600528

47. Maurin T, Saillan-Barreau C, Cousin B, Casteilla L, Doglio A, Pénicaud L. Tumor necrosis factor-alpha stimulates HIV-1 production in primary culture of human adipocytes. Exp Cell Res. 2005;304: 544–51. doi: 10.1016/j.yexcr.2004.12.003 15748898

48. Agarwal N, Iyer D, Patel SG, Sekhar R V, Phillips TM, Schubert U, et al. HIV-1 Vpr induces adipose dysfunction in vivo through reciprocal effects on PPAR/GR co-regulation. Sci Transl Med. 2013;5: 213ra164. doi: 10.1126/scitranslmed.3007148

49. Otake K, Omoto S, Yamamoto T, Okuyama H, Okada H, Okada N, et al. HIV-1 Nef protein in the nucleus influences adipogenesis as well as viral transcription through the peroxisome proliferator-activated receptors. AIDS. 2004;18: 189–98. 15075535

50. Cui HL, Ditiatkovski M, Kesani R, Bobryshev Y V, Liu Y, Geyer M, et al. HIV protein Nef causes dyslipidemia and formation of foam cells in mouse models of atherosclerosis. FASEB J. 2014;28: 2828–39. doi: 10.1096/fj.13-246876 24642731

51. Kaminski DA, Randall TD. Adaptive immunity and adipose tissue biology. Trends Immunol. 2010;31: 384–390. doi: 10.1016/j.it.2010.08.001 20817556

52. Ibrahim MM. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev. 2010;11: 11–18. doi: 10.1111/j.1467-789X.2009.00623.x 19656312

53. Chéret A, Le Grand R, Caufour P, Neildez O, Matheux F, Théodoro F, et al. Chemoattractant factors (IP-10, MIP-1alpha, IL-16) mRNA expression in mononuclear cells from different tissues during acute SIVmac251 infection of macaques. J Med Primatol. 1997;26: 19–26. 9271185

54. Chéret A, Le Grand R, Caufour P, Neildez O, Matheux F, Théodoro F, et al. RANTES, IFN-gamma, CCR1, and CCR5 mRNA expression in peripheral blood, lymph node, and bronchoalveolar lavage mononuclear cells during primary simian immunodeficiency virus infection of macaques. Virology. 1999;255: 285–93. doi: 10.1006/viro.1998.9558 10069954

55. Bernard-Stoecklin S, Gommet C, Corneau AB, Guenounou S, Torres C, Dejucq-Rainsford N, et al. Semen CD4+ T cells and macrophages are productively infected at all stages of SIV infection in macaques. PLoS Pathog. 2013;9: e1003810. doi: 10.1371/journal.ppat.1003810 24348253

56. Leone A, Rohankhedkar M, Okoye A, Legasse A, Axthelm MK, Villinger F, et al. Increased CD4+ T cell levels during IL-7 administration of antiretroviral therapy-treated simian immunodeficiency virus-positive macaques are not dependent on strong proliferative responses. J Immunol. 2010;185: 1650–9. doi: 10.4049/jimmunol.0902626 20622118

57. Sathaliyawala T, Kubota M, Yudanin N, Turner D, Camp P, Thome JJC, et al. Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets. Immunity. Elsevier Inc.; 2013;38: 187–97. doi: 10.1016/j.immuni.2012.09.020 23260195

58. Gebhardt T, Wakim LM, Eidsmo L, Reading PC, Heath WR, Carbone FR. Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nat Immunol. 2009;10: 524–30. doi: 10.1038/ni.1718 19305395

59. Dalmas E, Clément K, Guerre-Millo M. Defining macrophage phenotype and function in adipose tissue. Trends Immunol. 2011;32: 307–14. doi: 10.1016/j.it.2011.04.008 21616718

60. Vidal F, Domingo P, Villarroya F, Giralt M, López-Dupla M, Gutiérrez M, et al. Adipogenic/lipid, inflammatory, and mitochondrial parameters in subcutaneous adipose tissue of untreated HIV-1-infected long-term nonprogressors: significant alterations despite low viral burden. J Acquir Immune Defic Syndr. 2012;61: 131–7. doi: 10.1097/QAI.0b013e31825c3a68 22580565

61. Muthumani K, Choo AY, Premkumar A, Hwang DS, Thieu KP, Desai BM, et al. Human immunodeficiency virus type 1 (HIV-1) Vpr-regulated cell death: insights into mechanism. Cell Death Differ. 2005;12 Suppl 1: 962–70. doi: 10.1038/sj.cdd.4401583 15832179

62. Shrivastav S, Kino T, Cunningham T, Ichijo T, Schubert U, Heinklein P, et al. Human immunodeficiency virus (HIV)-1 viral protein R suppresses transcriptional activity of peroxisome proliferator-activated receptor {gamma} and inhibits adipocyte differentiation: implications for HIV-associated lipodystrophy. Mol Endocrinol. 2008;22: 234–47. doi: 10.1210/me.2007-0124 17932108

63. Casteilla L, Planat-Benard V, Laharrague P, Cousin B. Adipose-derived stromal cells: Their identity and uses in clinical trials, an update. World J Stem Cells. 2011;3: 25–33. doi: 10.4252/wjsc.v3.i4.25 21607134

64. Baglioni S, Francalanci M, Squecco R, Lombardi A, Cantini G, Angeli R, et al. Characterization of human adult stem-cell populations isolated from visceral and subcutaneous adipose tissue. doi: 10.1096/fj.08-126946

65. Nazari-Shafti TZ, Freisinger E, Roy U, Bulot CT, Senst C, Dupin CL, et al. Mesenchymal stem cell derived hematopoietic cells are permissive to HIV-1 infection. Retrovirology. 2011;8: 3. doi: 10.1186/1742-4690-8-3 21226936

66. Mannioui A, Bourry O, Sellier P, Delache B, Brochard P, Andrieu T, et al. Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques. Retrovirology. 2009;6: 106. doi: 10.1186/1742-4690-6-106 19930655

67. Moreau M, Le Tortorec A, Deleage C, Brown C, Denis H, Satie A-P, et al. Impact of short-term HAART initiated during the chronic stage or shortly post-exposure on SIV infection of male genital organs. PLoS One. 2012;7: e37348. doi: 10.1371/journal.pone.0037348 22615988

68. Lindqvist M, van Lunzen J, Soghoian DZ, Kuhl BD, Ranasinghe S, Kranias G, et al. Expansion of HIV-specific T follicular helper cells in chronic HIV infection. J Clin Invest. 2012;122: 3271–80. doi: 10.1172/JCI64314 22922259

69. Fukazawa Y, Lum R, Okoye AA, Park H, Matsuda K, Bae JY, et al. B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers. Nat Med. 2015;21: 132–9. doi: 10.1038/nm.3781 25599132

70. Lucas S, Taront S, Magnan C, Fauconnier L, Delacre M, Macia L, et al. Interleukin-7 regulates adipose tissue mass and insulin sensitivity in high-fat diet-fed mice through lymphocyte-dependent and independent mechanisms. PLoS One. 2012;7: e40351. doi: 10.1371/journal.pone.0040351 22768283

71. Lam YY, Mitchell AJ, Holmes AJ, Denyer GS, Gummesson A, Caterson ID, et al. Role of the gut in visceral fat inflammation and metabolic disorders. Obesity (Silver Spring). 2011;19: 2113–20. doi: 10.1038/oby.2011.68

72. Gregor MF, Hotamisligil S. Inflammatory Mechanisms in Obesity. Annu Rev Immunol. 2011;29: 415–445. doi: 10.1146/annurev-immunol-031210-101322 21219177

73. Couturier J, Suliburk JW, Brown JM, Luke DJ, Agarwal N, Yu X, et al. Human adipose tissue as a reservoir for memory CD4+ T cells and HIV. AIDS. 2015;29: 667–74. doi: 10.1097/QAD.0000000000000599 25849830

74. Duffaut C, Zakaroff-girard A, Bourlier V, Decaunes P, Maumus M, Chiotasso P, et al. Interplay Between Human Adipocytes and T Lymphocytes. 2009; 1608–1614. doi: 10.1161/ATVBAHA.109.192583 19644053

75. Vernochet C, Azoulay S, Duval D, Guedj R, Cottrez F, Vidal H, et al. Human immunodeficiency virus protease inhibitors accumulate into cultured human adipocytes and alter expression of adipocytokines. J Biol Chem. 2005;280: 2238–43. doi: 10.1074/jbc.M408687200 15525648

76. De Wit S, Delforge M, Necsoi CV, Clumeck N. Downregulation of CD38 activation markers by atorvastatin in HIV patients with undetectable viral load. AIDS. 2011;25: 1332–3. doi: 10.1097/QAD.0b013e328347c083 21508802

77. Calza L, Trapani F, Bartoletti M, Manfredi R, Colangeli V, Borderi M, et al. Statin therapy decreases serum levels of high-sensitivity C-reactive protein and tumor necrosis factor-α in HIV-infected patients treated with ritonavir-boosted protease inhibitors. HIV Clin Trials. 13: 153–61. doi: 10.1310/hct1303-153 22592095

78. Fuente-Martín E, Argente-Arizón P, Ros P, Argente J, Chowen JA. Sex differences in adipose tissue: It is not only a question of quantity and distribution. Adipocyte. 2013;2: 128–34. doi: 10.4161/adip.24075 23991358

79. Hofmann-Lehmann R, Swenerton RK, Liska V, Leutenegger CM, Lutz H, McClure HM, et al. Sensitive and robust one-tube real-time reverse transcriptase-polymerase chain reaction to quantify SIV RNA load: comparison of one- versus two-enzyme systems. AIDS Res Hum Retroviruses. 2000;16: 1247–57. doi: 10.1089/08892220050117014 10957722

80. Kornfeld C, Ploquin MJ-Y, Pandrea I, Faye A, Onanga R, Apetrei C, et al. Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS. J Clin Invest. 2005;115: 1082–91. doi: 10.1172/JCI23006 15761496

81. Karlsson I, Malleret B, Brochard P, Delache B, Calvo J, Le Grand R, et al. Dynamics of T-cell responses and memory T cells during primary simian immunodeficiency virus infection in cynomolgus macaques. J Virol. 2007;81: 13456–68. doi: 10.1128/JVI.01619-07 17913797

82. Avettand-Fenoel V, Prazuck T, Hocqueloux L, Melard A, Michau C, Kerdraon R, et al. HIV-DNA in rectal cells is well correlated with HIV-DNA in blood in different groups of patients, including long-term non-progressors. AIDS. 2008;22: 1880–2. doi: 10.1097/QAD.0b013e32830fbdbc 18753926

83. Avettand-Fènoël V, Chaix M-L, Blanche S, Burgard M, Floch C, Toure K, et al. LTR real-time PCR for HIV-1 DNA quantitation in blood cells for early diagnosis in infants born to seropositive mothers treated in HAART area (ANRS CO 01). J Med Virol. 2009;81: 217–23. doi: 10.1002/jmv.21390 19107966

84. Bacchus C, Cheret A, Avettand-Fenoël V, Nembot G, Mélard A, Blanc C, et al. A single HIV-1 cluster and a skewed immune homeostasis drive the early spread of HIV among resting CD4+ cell subsets within one month post-infection. PLoS One. 2013;8: e64219. doi: 10.1371/journal.pone.0064219 23691172

85. Canaud G, Dejucq-Rainsford N, Avettand-Fenoël V, Viard J-P, Anglicheau D, Bienaimé F, et al. The kidney as a reservoir for HIV-1 after renal transplantation. J Am Soc Nephrol. 2014;25: 407–19. doi: 10.1681/ASN.2013050564 24309185

86. Pudney J, Anderson D. Orchitis and human immunodeficiency virus type 1 infected cells in reproductive tissues from men with the acquired immune deficiency syndrome. Am J Pathol. 1991;139: 149–60. 1853930

87. Le Tortorec A, Satie A-P, Denis H, Rioux-Leclercq N, Havard L, Ruffault A, et al. Human prostate supports more efficient replication of HIV-1 R5 than X4 strains ex vivo. Retrovirology. 2008;5: 119. doi: 10.1186/1742-4690-5-119 19117522

88. Matusali G, Dereuddre-Bosquet N, Le Tortorec A, Moreau M, Satie A-P, Mahé D, et al. Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy. J Virol. 2015;89: 5772–87. doi: 10.1128/JVI.03628-14 25833047