Abstract
The mucosal surfaces of the genital and gastrointestinal tracts are the routes by which HIV-1 is acquired, excluding persons infected parenterally. Identification of the mucosal target cells and the receptors by which HIV-1 enters these cells is fundamental to elucidating the biology of HIV-1 transmission. The mucosal target cells include epithelial cells, dendritic cells, Langerhans cells, CD4+ T-cells, macrophages and even mast cells, but the contribution of each cell type is highly dependent on the mucosal surface - genital versus gastrointestinal. Importantly, mucosal target cells may also play key roles in the immunobiology and latency of HIV-1 infection. Given the pivotal role of mucosal cells in HIV-1 transmission and pathogenesis, an effective vaccine to bring the HIV-1 pandemic under control must be effective at the level of the key target cells in both the genital and gastrointestinal mucosae.
Keywords: Mucosal HIV-1, epithelial cell, macrophage, T-cell, dendritic cell, mast cell.
[2]
Royce RA, Sena A, Cates W Jr, Cohen MS. Sexual transmission of HIV. N Engl J Med 1997; 336(15): 1072-8.
[3]
Shattock RJ, Moore JP. Inhibiting sexual transmission of HIV-1 infection. Nat Rev Microbiol 2003; 1(1): 25-34.
[4]
Hladik F, McElrath MJ. Setting the stage: Host invasion by HIV. Nat Rev Immunol 2008; 8(6): 447-57.
[5]
Lai SK, Hida K, Shukair S, et al. Human immunodeficiency virus type 1 is trapped by acidic but not by neutralized human cervicovaginal mucus. J Virol 2009; 83(21): 11196-200.
[6]
Shukair SA, Allen SA, Cianci GC, et al. Human cervicovaginal mucus contains an activity that hinders HIV-1 movement. Mucosal Immunol 2013; 6(2): 427-34.
[7]
Bobardt MD, Chatterji U, Selvarajah S, et al. Cell-free human immunodeficiency virus type 1 transcytosis through primary genital epithelial cells. J Virol 2007; 81(1): 395-405.
[8]
Stoddard E, Cannon G, Ni H, et al. gp340 expressed on human genital epithelia binds HIV-1 envelope protein and facilitates viral transmission. J Immunol 2007; 179(5): 3126-32.
[9]
Stoddard E, Ni H, Cannon G, et al. gp340 promotes transcytosis of human immunodeficiency virus type 1 in genital tract-derived cell lines and primary endocervical tissue. J Virol 2009; 83(17): 8596-603.
[10]
Patyka M, Malamud D, Weissman D, Abrams WR, Kurago Z. Periluminal distribution of HIV-binding target cells and Gp340 in the oral, cervical and sigmoid/rectal mucosae: A mapping study. PLoS One 2015; 10(7): e0132942.
[11]
Asin SN, Fanger MW, Wildt-Perinic D, Ware PL, Wira CR, Howell AL. Transmission of HIV-1 by primary human uterine epithelial cells and stromal fibroblasts. J Infect Dis 2004; 190(2): 236-45.
[12]
Asin SN, Wildt-Perinic D, Mason SI, Howell AL, Wira CR, Fanger MW. Human immunodeficiency virus type 1 infection of human uterine epithelial cells: Viral shedding and cell contact-mediated infectivity. J Infect Dis 2003; 187(10): 1522-33.
[13]
Wu Z, Chen Z, Phillips DM. Human genital epithelial cells capture cell-free human immunodeficiency virus type 1 and transmit the virus to CD4+ Cells: Implications for mechanisms of sexual transmission. J Infect Dis 2003; 188(10): 1473-82.
[14]
Micsenyi AM, Zony C, Alvarez RA, Durham ND, Chen BK, Klotman ME. Postintegration HIV-1 infection of cervical epithelial cells mediates contact-dependent productive infection of T cells. J Infect Dis 2013; 208(11): 1756-67.
[15]
Dezzutti CS, Guenthner PC, Cummins JE Jr, et al. Cervical and prostate primary epithelial cells are not productively infected but sequester human immunodeficiency virus type 1. J Infect Dis 2001; 183(8): 1204-13.
[16]
Fontenot D, He H, Hanabuchi S, et al. TSLP production by epithelial cells exposed to immunodeficiency virus triggers DC-mediated mucosal infection of CD4+ T cells. Proc Natl Acad Sci USA 2009; 106(39): 16776-81.
[17]
Howell AL, Edkins RD, Rier SE, et al. Human immunodeficiency virus type 1 infection of cells and tissues from the upper and lower human female reproductive tract. J Virol 1997; 71(5): 3498-506.
[18]
Tan X, Pearce-Pratt R, Phillips DM. Productive infection of a cervical epithelial cell line with human immunodeficiency virus: Implications for sexual transmission. J Virol 1993; 67(11): 6447-52.
[19]
Tan X, Phillips DM. CAT-transfected epithelial cells provide evidence for a CD4 independent pathway of HIV infection. J Reprod Immunol 1998; 41(1-2): 307-19.
[20]
Phillips DM, Zacharopoulos VR, Tan X, Pearce-Pratt R. Mechanisms of sexual transmission of HIV: Does HIV infect intact epithelia? Trends Microbiol 1994; 2(11): 454-8.
[21]
Yeaman GR, White HD, Howell A, Prabhala R, Wira CR. The mucosal immune system in the human female reproductive tract:
Potential insights into the heterosexual transmission of HIV. AIDS
Res Hum Retroviruses 1998; 14 Suppl: 1S57-62.
[22]
Greenhead P, Hayes P, Watts PS, Laing KG, Griffin GE, Shattock RJ. Parameters of human immunodeficiency virus infection of human cervical tissue and inhibition by vaginal virucides. J Virol 2000; 74(12): 5577-86.
[23]
Miller CJ, Vogel P, Alexander NJ, Dandekar S, Hendrickx AG, Marx PA. Pathology and localization of simian immunodeficiency virus in the reproductive tract of chronically infected male rhesus macaques. Lab Invest 1994; 70(2): 255-62.
[24]
Miller CJ. Localization of Simian immunodeficiency virus-infected cells in the genital tract of male and female Rhesus macaques. J Reprod Immunol 1998; 41(1-2): 331-9.
[25]
Shen R, Richter HE, Clements RH, et al. Macrophages in vaginal but not intestinal mucosa are monocyte-like and permissive to human immunodeficiency virus type 1 infection. J Virol 2009; 83(7): 3258-67.
[26]
Shen R, Richter HE, Smith PD. Early HIV-1 target cells in human vaginal and ectocervical mucosa. Am J Reprod Immunol 2011; 65(3): 261-7.
[27]
Stieh DJ, Matias E, Xu H, et al. Th17 cells are preferentially infected very early after vaginal transmission of SIV in macaques. Cell Host Microbe 2016; 19(4): 529-40.
[28]
Hu J, Pope M, Brown C, O’Doherty U, Miller CJ. Immunophenotypic characterization of simian immunodeficiency virus-infected dendritic cells in cervix, vagina, and draining lymph nodes of rhesus monkeys. Lab Invest 1998; 78(4): 435-51.
[29]
Stieh DJ, Maric D, Kelley ZL, et al. Vaginal challenge with an SIV-based dual reporter system reveals that infection can occur throughout the upper and lower female reproductive tract. PLoS Pathog 2014; 10(10): e1004440.
[30]
Collins KB, Patterson BK, Naus GJ, Landers DV, Gupta P. Development of an in vitro organ culture model to study transmission of HIV-1 in the female genital tract. Nat Med 2000; 6(4): 475-9.
[31]
Gupta P, Collins KB, Ratner D, et al. Memory CD4+ T cells are the earliest detectable human immunodeficiency virus type 1 (HIV-1)-infected cells in the female genital mucosal tissue during HIV-1 transmission in an organ culture system. J Virol 2002; 76(19): 9868-76.
[32]
Zhang Z, Schuler T, Zupancic M, et al. Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. Science 1999; 286(5443): 1353-7.
[33]
Fischetti L, Barry SM, Hope TJ, Shattock RJ. HIV-1 infection of human penile explant tissue and protection by candidate microbicides. AIDS 2009; 23(3): 319-28.
[34]
Ma ZM, Dutra J, Fritts L, Miller CJ. Lymphatic dissemination of simian immunodeficiency virus after penile inoculation. J Virol 2016; 90(8): 4093-104.
[35]
Veazey RS, Marx PA, Lackner AA. Vaginal CD4+ T cells express high levels of CCR5 and are rapidly depleted in simian immunodeficiency virus infection. J Infect Dis 2003; 187(5): 769-76.
[36]
Miller CJ, Vogel P, Alexander NJ, Sutjipto S, Hendrickx AG, Marx PA. Localization of SIV in the genital tract of chronically infected female rhesus macaques. Am J Pathol 1992; 141(3): 655-60.
[37]
Pudney J, Quayle AJ, Anderson DJ. Immunological microenviron- ments in the human vagina and cervix: Mediators of cellular immunity are concentrated in the cervical transformation zone. Biol Reprod 2005; 73(6): 1253-63.
[38]
Maher D, Wu X, Schacker T, Horbul J, Southern P. HIV binding, penetration, and primary infection in human cervicovaginal tissue. Proc Natl Acad Sci USA 2005; 102(32): 11504-9.
[39]
Hladik F, Sakchalathorn P, Ballweber L, et al. Initial events in establishing vaginal entry and infection by human immunodeficiency virus type-1. Immunity 2007; 26(2): 257-70.
[40]
Saba E, Grivel JC, Vanpouille C, et al. HIV-1 sexual transmission: early events of HIV-1 infection of human cervico-vaginal tissue in an optimized ex vivo model. Mucosal Immunol 2010; 3(3): 280-90.
[41]
Quayle AJ, Kourtis AP, Cu-Uvin S, et al. T-lymphocyte profile and total and virus-specific immunoglobulin concentrations in the cervix of HIV-1-infected women. J Acquir Immune Defic Syndr 2007; 44(3): 292-8.
[42]
Jaspan HB, Liebenberg L, Hanekom W, et al. Immune activation in the female genital tract during HIV infection predicts mucosal CD4 depletion and HIV shedding. J Infect Dis 2011; 204(10): 1550-6.
[43]
Pope M. Mucosal dendritic cells and immunodeficiency viruses. J Infect Dis 1999; 179(Suppl. 3): S427-30.
[44]
Teleshova N, Frank I, Pope M. Immunodeficiency virus exploitation of dendritic cells in the early steps of infection. J Leukoc Biol 2003; 74(5): 683-90.
[45]
Hu Q, Frank I, Williams V, et al. Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue. J Exp Med 2004; 199(8): 1065-75.
[46]
Spira AI, Marx PA, Patterson BK, et al. Cellular targets of infection and route of viral dissemination after an intravaginal inoculation of simian immunodeficiency virus into rhesus macaques. J Exp Med 1996; 183(1): 215-25.
[47]
Piguet V, Steinman RM. The interaction of HIV with dendritic cells: Outcomes and pathways. Trends Immunol 2007; 28(11): 503-10.
[48]
Wu L. KewalRamani VN. Dendritic-cell interactions with HIV: Infection and viral dissemination. Nat Rev Immunol 2006; 6(11): 859-68.
[49]
Hu J, Gardner MB, Miller CJ. Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells. J Virol 2000; 74(13): 6087-95.
[50]
Cameron P, Pope M, Granelli-Piperno A, Steinman RM. Dendritic cells and the replication of HIV-1. J Leukoc Biol 1996; 59(2): 158-71.
[51]
David SA, Smith MS, Lopez GJ, et al. Selective transmission of R5-tropic HIV type 1 from dendritic cells to resting CD4+ T cells. AIDS Res Hum Retroviruses 2001; 17(1): 59-68.
[52]
Cameron PU, Freudenthal PS, Barker JM, Gezelter S, Inaba K, Steinman RM. Dendritic cells exposed to human immunodeficiency virus type-1 transmit a vigorous cytopathic infection to CD4+ T cells. Science 1992; •••: 257383-7.
[53]
Pope M, Betjes MGH, Romani N, et al. Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1. Cell 1994; •••: 78389-98.
[54]
Hu J, Miller CJ, O’Doherty U, Marx PA, Pope M. The dendritic cell-T cell milieu of the lymphoid tissue of the tonsil provides a locale in which SIV can reside and propagate at chronic stages of infection. AIDS Res Hum Retroviruses 1999; 15(14): 1305-14.
[55]
Kawamura T, Gulden FO, Sugaya M, et al. R5 HIV productively infects Langerhans cells, and infection levels are regulated by compound CCR5 polymorphisms. Proc Natl Acad Sci USA 2003; 100(14): 8401-6.
[56]
Ganor Y, Bomsel M. HIV-1 transmission in the male genital tract. Am J Reprod Immunol 2011; 65(3): 284-91.
[57]
Ganor Y, Zhou Z, Tudor D, et al. Within 1 h, HIV-1 uses viral synapses to enter efficiently the inner, but not outer, foreskin mucosa and engages Langerhans-T cell conjugates. Mucosal Immunol 2010; 3(5): 506-22.
[58]
Miller CJ, Li Q, Abel K, et al. Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. J Virol 2005; 79(14): 9217-27.
[59]
Miller CJ, Hu J. T cell-tropic Simian Immunodeficiency Virus (SIV) and simian-human immunodeficiency viruses are readily transmitted by vaginal inoculation of rhesus macaques, and Langerhans’ cells of the female genital tract are infected with SIV. J Infect Dis 1999; 179(Suppl. 3): S413-7.
[60]
Reece JC, Handley AJ, Anstee EJ, Morrison WA, Crowe SM, Cameron PU. HIV-1 selection by epidermal dendritic cells during transmission across human skin. J Exp Med 1998; 187(10): 1623-31.
[61]
Blauvelt A, Glushakova S, Margolis LB. HIV-infected human Langerhans cells transmit infection to human lymphoid tissue ex vivo. AIDS 2000; 14(6): 647-51.
[62]
Ballweber L, Robinson B, Kreger A, et al. Vaginal langerhans cells nonproductively transporting HIV-1 mediate infection of T cells. J Virol 2011; 85(24): 13443-7.
[63]
Shen R, Kappes JC, Smythies LE, Richter HE, Novak L, Smith PD. Vaginal myeloid dendritic cells transmit founder HIV-1. J Virol 2014; 88(13): 7683-8.
[64]
Kedzierska K, Crowe SM, Turville S, Cunningham AL. The influence of cytokines, chemokines and their receptors on HIV-1 replication in monocytes and macrophages. Rev Med Virol 2003; 13(1): 39-56.
[65]
Gorry PR, Churchill M, Crowe SM, Cunningham AL, Gabuzda D. Pathogenesis of macrophage tropic HIV-1. Curr HIV Res 2005; 3(1): 53-60.
[66]
Carter CA, Ehrlich LS. Cell biology of HIV-1 infection of macrophages. Annu Rev Microbiol 2008; 62: 425-43.
[67]
Koppensteiner H, Brack-Werner R, Schindler M. Macrophages and their relevance in Human Immunodeficiency Virus Type I infection. Retrovirology 2012; 9: 82.
[68]
Cobos-Jimenez V, Booiman T, Hamann J, Kootstra NA. Macrophages and HIV-1. Curr Opin HIV AIDS 2011; 6(5): 385-90.
[69]
Kumar A, Abbas W, Herbein G. HIV-1 latency in monocytes/macrophages. Viruses 2014; 6(4): 1837-60.
[70]
Watters SA, Mlcochova P, Gupta RK. Macrophages: the neglected barrier to eradication. Curr Opin Infect Dis 2013; 26(6): 561-6.
[71]
Collman R, Hassan NF, Walker R, et al. Infection of monocyte-derived macrophages with Human Immunodeficiency Virus type 1 (HIV-1). Monocyte-tropic and lymphocyte-tropic strains of HIV-1 show distinctive patterns of replication in a panel of cell types. J Exp Med 1989; 170(4): 1149-63.
[72]
Rich EA, Chen IS, Zack JA, Leonard ML, O’Brien WA. Increased susceptibility of differentiated mononuclear phagocytes to productive infection with human immunodeficiency virus-1 (HIV-1). J Clin Invest 1992; 89(1): 176-83.
[73]
Ganor Y, Zhou Z, Bodo J, et al. The adult penile urethra is a novel entry site for HIV-1 that preferentially targets resident urethral macrophages. Mucosal Immunol 2013; 6(4): 776-86.
[74]
Pomerantz RJ, de la Monte SM, Donegan SP, et al. Human Immunodeficiency Virus (HIV) infection of the uterine cervix. Ann Intern Med 1988; 108(3): 321-7.
[75]
Howell AL, Asin SN, Yeaman GR, Wira CR. HIV-1 infection of the female reproductive tract. Curr HIV/AIDS Rep 2005; 2(1): 35-8.
[76]
Sharova N, Swingler C, Sharkey M, Stevenson M. Macrophages archive HIV-1 virions for dissemination in trans. EMBO J 2005; 24(13): 2481-9.
[77]
Embretson J, Zupancic M, Beneke J, et al. Analysis of human immunodeficiency virus-infected tissues by amplification and in situ hybridization reveals latent and permissive infections at single-cell resolution. Proc Natl Acad Sci USA 1993; 90(1): 357-61.
[78]
Zhu T, Muthui D, Holte S, et al. Evidence for human immunodeficiency virus type 1 replication in vivo in CD14+ monocytes and its potential role as a source of virus in patients on highly active antiretroviral therapy. J Virol 2002; 76(2): 707-16.
[79]
Crowe S, Zhu T, Muller WA. The contribution of monocyte infection and trafficking to viral persistence, and maintenance of the viral reservoir in HIV infection. J Leukoc Biol 2003; 74(5): 635-41.
[80]
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(1): 149-60.
[81]
Quayle AJ, Xu C, Mayer KH, Anderson DJ. T lymphocytes and macrophages, but not motile spermatozoa, are a significant source of human immunodeficiency virus in semen. J Infect Dis 1997; 176(4): 960-8.
[82]
Phillips DM, Tan X, Perotti ME, Zacharopoulos VR. Mechanism of monocyte-macrophage-mediated transmission of HIV. AIDS Res Hum Retroviruses 1998; 14(Suppl. 1): S67-70.
[83]
Crowe SM, Sonza S. HIV-1 can be recovered from a variety of cells including peripheral blood monocytes of patients receiving highly active antiretroviral therapy: A further obstacle to eradication. J Leukoc Biol 2000; 68(3): 345-50.
[84]
Satomi M, Shimizu M, Shinya E, et al. Transmission of macrophage-tropic HIV-1 by breast-milk macrophages via DC-SIGN. J Infect Dis 2005; 191(2): 174-81.
[85]
Orenstein JM, Fox C, Wahl SM. Macrophages as a source of HIV during opportunistic infections. Science 1997; 276(5320): 1857-61.
[86]
Wahl SM, Greenwell-Wild T, Peng G, et al. Mycobacterium avium complex augments macrophage HIV-1 production and increases CCR5 expression. Proc Natl Acad Sci USA 1998; 95(21): 12574-9.
[87]
Wahl SM, Allen JB, McCartney-Francis N, et al. Macrophage- and astrocyte-derived transforming growth factor β as a mediator of central nervous system dysfunction in acquired immune deficiency syndrome. J Exp Med 1991; 173(4): 981-91.
[88]
Crowe SM, Mills J, Kirihara J, Boothman J, Marshall JA, McGrath MS. Full-length recombinant CD4 and recombinant gp120 inhibit fusion between HIV infected macrophages and uninfected CD4-expressing T-lymphoblastoid cells. AIDS Res Hum Retroviruses 1990; 6(8): 1031-7.
[89]
Groot F, Welsch S, Sattentau QJ. Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses. Blood 2008; 111(9): 4660-3.
[90]
Gousset K, Ablan SD, Coren LV, et al. Real-time visualization of HIV-1 GAG trafficking in infected macrophages. PLoS Pathog 2008; 4(3): e1000015.
[91]
Garaci E, Aquaro S, Lapenta C, et al. Anti-nerve growth factor Ab abrogates macrophage-mediated HIV-1 infection and depletion of CD4+ T lymphocytes in hu-SCID mice. Proc Natl Acad Sci USA 2003; 100(15): 8927-32.
[92]
Pollicita M, Schols D, Aquaro S, et al. Carbohydrate-Binding Agents (CBAs) inhibit HIV-1 infection in human primary Monocyte-Derived Macrophages (MDMs) and efficiently prevent MDM-directed viral capture and subsequent transmission to CD4+ T lymphocytes. Virology 2008; 370(2): 382-91.
[93]
Badley AD, Dockrell D, Simpson M, et al. Macrophage-dependent apoptosis of CD4+ T lymphocytes from HIV-infected individuals is mediated by FasL and tumor necrosis factor. J Exp Med 1997; 185(1): 55-64.
[94]
Schmidtmayerova H, Nottet HSLM, Nuovo G, et al. Human immunodeficiency virus type 1 infection alters chemokine b peptide expression in human monocytes: Implications for recruitment of leukocytes into brain and lymph nodes. Proc Natl Acad Sci USA 1996; 93(2): 700-4.
[95]
Smith PD, Ohura K, Masur H, Lane HC, Fauci AS, Wahl SM. Monocyte function in the acquired immune deficiency syndrome: Defective chemotaxis. J Clin Invest 1984; 74(6): 2121-8.
[96]
Hirsch VM, Sharkey ME, Brown CR, Brichacek B, Goldstein S, Wakefield J, et al. Vpx is required for dissemination and pathogenesis of SIV(SM) PBj: Evidence of macrophage-dependent viral amplification. Nat Med 1998; 4(12): 1401-8.
[97]
Smith PD, Fox CH, Masur H, Winter HS, Alling DW. Quantitative analysis of mononuclear cells expressing human immunodeficiency virus type 1 RNA in esophageal mucosa. J Exp Med 1994; 180(4): 1541-6.
[98]
Lee SH, Starkey PM, Gordon S. Quantitative analysis of total macrophage content in adult mouse tissues. Immunochemical studies with monoclonal antibody F4/80. J Exp Med 1985; 161(3): 475-89.
[99]
Pabst R, Russell MW, Brandtzaeg P. Tissue distribution of lymphocytes and plasma cells and the role of the gut. Trends Immunol 2008; 29(5): 206-208; author reply 209-210.
[100]
Bomsel M. Transcytosis of infectious human immunodeficiency virus across a tight human epithelial cell line barrier. Nat Med 1997; 3(1): 42-7.
[101]
Alfsen A, Bomsel M. HIV-1 gp41 envelope residues 650-685 exposed on native virus act as a lectin to bind epithelial cell galactosyl ceramide. J Biol Chem 2002; 277(28): 25649-59.
[102]
Zhou Z, Barry de Longchamps N, et al. HIV-1 efficient entry in inner foreskin is mediated by elevated CCL5/RANTES that recruits T cells and fuels conjugate formation with Langerhans cells. PLoS Pathog 2011; 7(6): e1002100.
[103]
Alfsen A, Yu H, Magerus-Chatinet A, Schmitt A, Bomsel M. HIV-1-infected blood mononuclear cells form an integrin- and agrin-dependent viral synapse to induce efficient HIV-1 transcytosis across epithelial cell monolayer. Mol Biol Cell 2005; 16(9): 4267-79.
[104]
Bomsel M, Tudor D, Drillet AS, et al. Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges. Immunity 2011; 34(2): 269-80.
[105]
Shen R, Kaplan MH. The homeostasis but not the differentiation of T cells is regulated by p27(Kip1). J Immunol 2002; 169(2): 714-21.
[106]
Leroux-Roels G, Maes C, Clement F, et al. Randomized phase I: Safety, immunogenicity and mucosal antiviral activity in young healthy women vaccinated with HIV-1 Gp41 P1 peptide on virosomes. PLoS One 2013; 8(2): e55438.
[107]
Meng G, Wei X, Wu X, et al. Primary intestinal epithelial cells selectively transfer R5 HIV-1 to CCR5+ cells. Nat Med 2002; 8(2): 150-6.
[108]
Mabbott NA, Donaldson DS, Ohno H, Williams IR, Mahajan A. Microfold (M) cells: important immunosurveillance posts in the intestinal epithelium. Mucosal Immunol 2013; 6(4): 666-77.
[109]
Amerongen HM, Weltzin R, Farnet CM, Michetti P, Haseltine WA, Neutra MR. Transepithelial transport of HIV-1 by intestinal M cells: A mechanism for transmission of AIDS. JAIDS 1991; 4(8): 760-5.
[110]
Smith PD, Meng G, Salazar-Gonzalez JF, Shaw GM. Macrophage HIV-1 infection and the gastrointestinal tract reservoir. J Leukoc Biol 2003; 74(5): 642-9.
[111]
Jameson B, Baribaud F, Pohlmann S, et al. Expression of DC-SIGN by dendritic cells of intestinal and genital mucosae in humans and rhesus macaques. J Virol 2002; 76(4): 1866-75.
[112]
Shen R, Smythies LE, Clements RH, Novak L, Smith PD. Dendritic cells transmit HIV-1 through human small intestinal mucosa. J Leukoc Biol 2010; 87(4): 663-70.
[113]
Keele BF, Giorgi EE, Salazar-Gonzalez JF, et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci USA 2008; 105(21): 7552-7.
[114]
Stone M, Keele BF, Ma ZM, et al. A limited number of Simian Immunodeficiency Virus (SIV) env variants are transmitted to rhesus macaques vaginally inoculated with SIVmac251. J Virol 2010; 84(14): 7083-95.
[115]
Brenchley JM, Schacker TW, Ruff LE, et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 2004; 200(6): 749-59.
[116]
Guadalupe M, Reay E, Sankaran S, et al. Severe CD4+ T cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol 2003; 77(21): 11708-17.
[117]
Li Q, Duan L, Estes JD, et al. Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature 2005; 434(7037): 1148-52.
[118]
Mattapallil JJ, Douek DC, Hill B, Nishimura Y, Martin M, Roederer M. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 2005; 434(7037): 1093-7.
[119]
Mehandru S, Poles MA, Tenner-Racz K, et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med 2004; 200(6): 761-70.
[120]
Veazey RS, DeMaria M, Chalifoux LV, et al. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 1998; 280(5362): 427-31.
[121]
Veazey RS, Tham IC, Mansfield KG, et al. Identifying the target cell in primary Simian Immunodeficiency Virus (SIV) infection: Highly activated memory CD4(+) T cells are rapidly eliminated in early SIV infection in vivo. J Virol 2000; 74(1): 57-64.
[122]
Smit-McBride Z, Mattapallil JJ, McChesney M, Ferrick D, Dandekar S. Gastrointestinal T lymphocytes retain high potential for cytokine responses but have severe CD4(+) T-cell depletion at all stages of simian immunodeficiency virus infection compared to peripheral lymphocytes. J Virol 1998; 72(8): 6646-56.
[123]
Mehandru S, Poles MA, Tenner-Racz K, et al. Mechanisms of gastrointestinal CD4+ T-cell depletion during acute and early human immunodeficiency virus type 1 infection. J Virol 2007; 81(2): 599-612.
[124]
Lee SH, Starkey PM, Gordon S. Quantitative analysis of total macrophage content in adult mouse tissues: Immunochemical studies with monoclonal antibody F4/80. J Exp Med 1985; 161(3): 475-89.
[125]
Smith PD, Smythies LE, Shen R, Greenwell-Wild T, Gliozzi M, Wahl SM. Intestinal macrophages and response to microbial encroachment. Mucosal Immunol 2011; 4(1): 31-42.
[126]
Smith PD, Smythies LE, Mosteller-Barnum M, et al. Intestinal macrophages lack CD14 and CD89 and consequently are down-regulated for LPS- and IgA-mediated activities. J Immunol 2001; 167(5): 2651-6.
[127]
Smythies LE, Sellers M, Clements RH, et al. Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J Clin Invest 2005; 115(1): 66-75.
[128]
Smythies LE, Shen R, Bimczok D, et al. Inflammation anergy in human intestinal macrophages is due to Smad-induced IκBα expression and NF-κB inactivation. J Biol Chem 2010; 285(25): 19593-604.
[129]
Li L, Meng G, Graham MF, Shaw GM, Smith PD. Intestinal macrophages display reduced permissiveness to human immunodeficiency virus 1 and decreased surface CCR5. Gastroenterology 1999; 116(5): 1043-53.
[130]
Shen R, Meng G, Ochsenbauer C, et al. Stromal down-regulation of macrophage CD4/CCR5 expression and NF-κB activation mediates HIV-1 non-permissiveness in intestinal macrophages. PLoS Pathog 2011; 7(5): e1002060.
[131]
Griffin GE, Leung K, Folks TM, Kunkel S, Nabel GJ. Activation of HIV gene expression during monocyte differentiation by induction of NF-κB. Nature 1989; 339(6219): 70-3.
[132]
Li JM, Shen X, Hu PP, Wang XF. Transforming growth factor β stimulates the human immunodeficiency virus 1 enhancer and requires NF-κB activity. Mol Cell Biol 1998; 18(1): 110-21.
[133]
Roulston A, Lin R, Beauparlant P, Wainberg MA, Hiscott J. Regulation of human immunodeficiency virus type 1 and cytokine gene expression in myeloid cells by NF-κB/Rel transcription factors. Microbiol Rev 1995; 59(3): 481-505.
[134]
Dreikhausen U, Hiebenthal-Millow K, Bartels M, Resch K, Nourbakhsh M. NF-κB-repressing factor inhibits elongation of human immunodeficiency virus type 1 transcription by DRB sensitivity-inducing factor. Mol Cell Biol 2005; 25(17): 7473-83.
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