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J Virol. 1997 October; 71(10): 8001–8007.
PMCID: PMC192162

Human immunodeficiency virus type 1 strains of subtypes B and E replicate in cutaneous dendritic cell-T-cell mixtures without displaying subtype-specific tropism.


A report that genetic subtype E human immunodeficiency virus type 1 (HIV-1) strains display a preferential tropism for Langerhans cells (epidermal dendritic cells [DCs]) compared to genetic subtype B strains suggested a possible explanation for the rapid heterosexual spread of subtype E strains in Thailand (L. E. Soto-Ramirez et al., Science 271:1291-1293, 1996). In an independent system, we applied subtype E and B isolates to skin leukocytes, since skin is a relevant model for the histologically comparable surfaces of the vagina and ectocervix. Isolates of both HIV-1 subtypes infected DC-T-cell mixtures, and no subtype-specific pattern of infection was observed. Purified DCs did not support the replication of strains of either subtype B or E. Our findings do not support the conclusion that subtype E strains have a preferential tropism for DCs, suggesting that other explanations for the rapid heterosexual spread of subtype E strains in Asia should be considered.

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Selected References

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  • Artenstein AW, VanCott TC, Mascola JR, Carr JK, Hegerich PA, Gaywee J, Sanders-Buell E, Robb ML, Dayhoff DE, Thitivichianlert S, et al. Dual infection with human immunodeficiency virus type 1 of distinct envelope subtypes in humans. J Infect Dis. 1995 Apr;171(4):805–810. [PubMed]
  • Austyn JM, Kupiec-Weglinski JW, Hankins DF, Morris PJ. Migration patterns of dendritic cells in the mouse. Homing to T cell-dependent areas of spleen, and binding within marginal zone. J Exp Med. 1988 Feb 1;167(2):646–651. [PMC free article] [PubMed]
  • Ayehunie S, Groves RW, Bruzzese AM, Ruprecht RM, Kupper TS, Langhoff E. Acutely infected Langerhans cells are more efficient than T cells in disseminating HIV type 1 to activated T cells following a short cell-cell contact. AIDS Res Hum Retroviruses. 1995 Aug;11(8):877–884. [PubMed]
  • Berger R, Gartner S, Rappersberger K, Foster CA, Wolff K, Stingl G. Isolation of human immunodeficiency virus type 1 from human epidermis: virus replication and transmission studies. J Invest Dermatol. 1992 Sep;99(3):271–277. [PubMed]
  • Bujdoso R, Hopkins J, Dutia BM, Young P, McConnell I. Characterization of sheep afferent lymph dendritic cells and their role in antigen carriage. J Exp Med. 1989 Oct 1;170(4):1285–1301. [PMC free article] [PubMed]
  • Cáceres CF, Hearst N. HIV/AIDS in Latin America and the Caribbean: an update. AIDS. 1996;10 (Suppl A):S43–S49. [PubMed]
  • Cameron P, Pope M, Granelli-Piperno A, Steinman RM. Dendritic cells and the replication of HIV-1. J Leukoc Biol. 1996 Feb;59(2):158–171. [PubMed]
  • 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 Jul 17;257(5068):383–387. [PubMed]
  • Cameron PU, Lowe MG, Crowe SM, O'Doherty U, Pope M, Gezelter S, Steinman RM. Susceptibility of dendritic cells to HIV-1 infection in vitro. J Leukoc Biol. 1994 Sep;56(3):257–265. [PubMed]
  • Charbonnier AS, Mallet F, Fiers MM, Desgranges C, Dezutter-Dambuyant C, Schmitt D. Detection of HIV-specific DNA sequences in epidermal Langerhans cells infected in vitro by means of a cell-free system. Arch Dermatol Res. 1994;287(1):36–41. [PubMed]
  • Chesebro B, Wehrly K, Nishio J, Perryman S. Macrophage-tropic human immunodeficiency virus isolates from different patients exhibit unusual V3 envelope sequence homogeneity in comparison with T-cell-tropic isolates: definition of critical amino acids involved in cell tropism. J Virol. 1992 Nov;66(11):6547–6554. [PMC free article] [PubMed]
  • Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, Wu L, Mackay CR, LaRosa G, Newman W, et al. The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell. 1996 Jun 28;85(7):1135–1148. [PubMed]
  • Daniels TE. Human mucosal Langerhans cells: postmortem identification of regional variations in oral mucosa. J Invest Dermatol. 1984 Jan;82(1):21–24. [PubMed]
  • Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, Goedert JJ, Buchbinder SP, Vittinghoff E, Gomperts E, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science. 1996 Sep 27;273(5283):1856–1862. [PubMed]
  • Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996 Jun 20;381(6584):661–666. [PubMed]
  • Mazzarelli JM, Mengus G, Davidson I, Ricciardi RP. The transactivation domain of adenovirus E1A interacts with the C terminus of human TAF(II)135. J Virol. 1997 Oct;71(10):7978–7983. [PMC free article] [PubMed]
  • Doranz BJ, Rucker J, Yi Y, Smyth RJ, Samson M, Peiper SC, Parmentier M, Collman RG, Doms RW. A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell. 1996 Jun 28;85(7):1149–1158. [PubMed]
  • Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashima KA, Cayanan C, Maddon PJ, Koup RA, Moore JP, et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature. 1996 Jun 20;381(6584):667–673. [PubMed]
  • Frankel SS, Tenner-Racz K, Racz P, Wenig BM, Hansen CH, Heffner D, Nelson AM, Pope M, Steinman RM. Active replication of HIV-1 at the lymphoepithelial surface of the tonsil. Am J Pathol. 1997 Jul;151(1):89–96. [PubMed]
  • Frankel SS, Wenig BM, Burke AP, Mannan P, Thompson LD, Abbondanzo SL, Nelson AM, Pope M, Steinman RM. Replication of HIV-1 in dendritic cell-derived syncytia at the mucosal surface of the adenoid. Science. 1996 Apr 5;272(5258):115–117. [PubMed]
  • Gebert A, Rothkötter HJ, Pabst R. M cells in Peyer's patches of the intestine. Int Rev Cytol. 1996;167:91–159. [PubMed]
  • Granelli-Piperno A, Moser B, Pope M, Chen D, Wei Y, Isdell F, O'Doherty U, Paxton W, Koup R, Mojsov S, et al. Efficient interaction of HIV-1 with purified dendritic cells via multiple chemokine coreceptors. J Exp Med. 1996 Dec 1;184(6):2433–2438. [PMC free article] [PubMed]
  • Huang Y, Paxton WA, Wolinsky SM, Neumann AU, Zhang L, He T, Kang S, Ceradini D, Jin Z, Yazdanbakhsh K, et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nat Med. 1996 Nov;2(11):1240–1243. [PubMed]
  • Inaba K, Metlay JP, Crowley MT, Steinman RM. Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J Exp Med. 1990 Aug 1;172(2):631–640. [PMC free article] [PubMed]
  • Kalish ML, Baldwin A, Raktham S, Wasi C, Luo CC, Schochetman G, Mastro TD, Young N, Vanichseni S, Rübsamen-Waigmann H, et al. The evolving molecular epidemiology of HIV-1 envelope subtypes in injecting drug users in Bangkok, Thailand: implications for HIV vaccine trials. AIDS. 1995 Aug;9(8):851–857. [PubMed]
  • Kalish ML, Luo CC, Weniger BG, Limpakarnjanarat K, Young N, Ou CY, Schochetman G. Early HIV type 1 strains in Thailand were not responsible for the current epidemic. AIDS Res Hum Retroviruses. 1994 Nov;10(11):1573–1575. [PubMed]
  • Knight SC, Macatonia SE, Patterson S. HIV I infection of dendritic cells. Int Rev Immunol. 1990;6(2-3):163–175. [PubMed]
  • Korber BT, Allen EE, Farmer AD, Myers GL. Heterogeneity of HIV-1 and HIV-2. AIDS. 1995;9 (Suppl A):S5–18. [PubMed]
  • Kunanusont C, Foy HM, Kreiss JK, Rerks-Ngarm S, Phanuphak P, Raktham S, Pau CP, Young NL. HIV-1 subtypes and male-to-female transmission in Thailand. Lancet. 1995 Apr 29;345(8957):1078–1083. [PubMed]
  • Langhoff E, Terwilliger EF, Bos HJ, Kalland KH, Poznansky MC, Bacon OM, Haseltine WA. Replication of human immunodeficiency virus type 1 in primary dendritic cell cultures. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7998–8002. [PubMed]
  • Lasky M, Perret JL, Peeters M, Bibollet-Ruche F, Liegeois F, Patrel D, Molinier S, Gras C, Delaporte E. Presence of multiple non-B subtypes and divergent subtype B strains of HIV-1 in individuals infected after overseas deployment. AIDS. 1997 Jan;11(1):43–51. [PubMed]
  • Liu LM, MacPherson GG. Antigen acquisition by dendritic cells: intestinal dendritic cells acquire antigen administered orally and can prime naive T cells in vivo. J Exp Med. 1993 May 1;177(5):1299–1307. [PMC free article] [PubMed]
  • Louwagie J, McCutchan FE, Peeters M, Brennan TP, Sanders-Buell E, Eddy GA, van der Groen G, Fransen K, Gershy-Damet GM, Deleys R, et al. Phylogenetic analysis of gag genes from 70 international HIV-1 isolates provides evidence for multiple genotypes. AIDS. 1993 Jun;7(6):769–780. [PubMed]
  • Ludewig B, Holzmeister J, Gentile M, Gelderblom HR, Rokos K, Becker Y, Pauli G. Replication pattern of human immunodeficiency virus type 1 in mature Langerhans cells. J Gen Virol. 1995 Jun;76(Pt 6):1317–1325. [PubMed]
  • Mascola JR, Louwagie J, McCutchan FE, Fischer CL, Hegerich PA, Wagner KF, Fowler AK, McNeil JG, Burke DS. Two antigenically distinct subtypes of human immunodeficiency virus type 1: viral genotype predicts neutralization serotype. J Infect Dis. 1994 Jan;169(1):48–54. [PubMed]
  • Mastro TD, de Vincenzi I. Probabilities of sexual HIV-1 transmission. AIDS. 1996;10 (Suppl A):S75–S82. [PubMed]
  • Mastro TD, Kunanusont C, Dondero TJ, Wasi C. Why do HIV-1 subtypes segregate among persons with different risk behaviors in South Africa and Thailand? AIDS. 1997 Jan;11(1):113–116. [PubMed]
  • McCutchan FE, Hegerich PA, Brennan TP, Phanuphak P, Singharaj P, Jugsudee A, Berman PW, Gray AM, Fowler AK, Burke DS. Genetic variants of HIV-1 in Thailand. AIDS Res Hum Retroviruses. 1992 Nov;8(11):1887–1895. [PubMed]
  • Miller CJ, Alexander NJ, Sutjipto S, Lackner AA, Gettie A, Hendrickx AG, Lowenstine LJ, Jennings M, Marx PA. Genital mucosal transmission of simian immunodeficiency virus: animal model for heterosexual transmission of human immunodeficiency virus. J Virol. 1989 Oct;63(10):4277–4284. [PMC free article] [PubMed]
  • Miller CJ, Alexander NJ, Vogel P, Anderson J, Marx PA. Mechanism of genital transmission of SIV: a hypothesis based on transmission studies and the location of SIV in the genital tract of chronically infected female rhesus macaques. J Med Primatol. 1992 Feb-May;21(2-3):64–68. [PubMed]
  • Miller CJ, McChesney M, Moore PF. Langerhans cells, macrophages and lymphocyte subsets in the cervix and vagina of rhesus macaques. Lab Invest. 1992 Nov;67(5):628–634. [PubMed]
  • Miller CJ, McGhee JR, Gardner MB. Mucosal immunity, HIV transmission, and AIDS. Lab Invest. 1993 Feb;68(2):129–145. [PubMed]
  • Moore JP, Cao Y, Leu J, Qin L, Korber B, Ho DD. Inter- and intraclade neutralization of human immunodeficiency virus type 1: genetic clades do not correspond to neutralization serotypes but partially correspond to gp120 antigenic serotypes. J Virol. 1996 Jan;70(1):427–444. [PMC free article] [PubMed]
  • Moore JP, McCutchan FE, Poon SW, Mascola J, Liu J, Cao Y, Ho DD. Exploration of antigenic variation in gp120 from clades A through F of human immunodeficiency virus type 1 by using monoclonal antibodies. J Virol. 1994 Dec;68(12):8350–8364. [PMC free article] [PubMed]
  • Moore JP, McKeating JA, Huang YX, Ashkenazi A, Ho DD. Virions of primary human immunodeficiency virus type 1 isolates resistant to soluble CD4 (sCD4) neutralization differ in sCD4 binding and glycoprotein gp120 retention from sCD4-sensitive isolates. J Virol. 1992 Jan;66(1):235–243. [PMC free article] [PubMed]
  • Nuovo GJ, Forde A, MacConnell P, Fahrenwald R. In situ detection of PCR-amplified HIV-1 nucleic acids and tumor necrosis factor cDNA in cervical tissues. Am J Pathol. 1993 Jul;143(1):40–48. [PubMed]
  • Ou CY, Takebe Y, Weniger BG, Luo CC, Kalish ML, Auwanit W, Yamazaki S, Gayle HD, Young NL, Schochetman G. Independent introduction of two major HIV-1 genotypes into distinct high-risk populations in Thailand. Lancet. 1993 May 8;341(8854):1171–1174. [PubMed]
  • Patterson S, Knight SC. Susceptibility of human peripheral blood dendritic cells to infection by human immunodeficiency virus. J Gen Virol. 1987 Apr;68(Pt 4):1177–1181. [PubMed]
  • Pavli P, Maxwell L, Van de Pol E, Doe F. Distribution of human colonic dendritic cells and macrophages. Clin Exp Immunol. 1996 Apr;104(1):124–132. [PubMed]
  • Pinchuk LM, Polacino PS, Agy MB, Klaus SJ, Clark EA. The role of CD40 and CD80 accessory cell molecules in dendritic cell-dependent HIV-1 infection. Immunity. 1994 Jul;1(4):317–325. [PubMed]
  • Pomerantz RJ, de la Monte SM, Donegan SP, Rota TR, Vogt MW, Craven DE, Hirsch MS. Human immunodeficiency virus (HIV) infection of the uterine cervix. Ann Intern Med. 1988 Mar;108(3):321–327. [PubMed]
  • Pope M, Betjes MG, Hirmand H, Hoffman L, Steinman RM. Both dendritic cells and memory T lymphocytes emigrate from organ cultures of human skin and form distinctive dendritic-T-cell conjugates. J Invest Dermatol. 1995 Jan;104(1):11–17. [PubMed]
  • Pope M, Betjes MG, Romani N, Hirmand H, Cameron PU, Hoffman L, Gezelter S, Schuler G, Steinman RM. Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1. Cell. 1994 Aug 12;78(3):389–398. [PubMed]
  • Pope M, Gezelter S, Gallo N, Hoffman L, Steinman RM. Low levels of HIV-1 infection in cutaneous dendritic cells promote extensive viral replication upon binding to memory CD4+ T cells. J Exp Med. 1995 Dec 1;182(6):2045–2056. [PMC free article] [PubMed]
  • Ramazzotti E, Marconi A, Re MC, Girolomoni G, Cenacchi G, Vignoli M, Zambruno G, Furlini G, La Placa M, Giannetti A. In vitro infection of human epidermal Langerhans' cells with HIV-1. Immunology. 1995 May;85(1):94–98. [PubMed]
  • Ramirez G, Braathen LR, Kunze RO, Gelderblom H. In vitro infection of human epidermal Langerhans cells with HIV. Adv Exp Med Biol. 1988;237:901–905. [PubMed]
  • Richters CD, Hoekstra MJ, van Baare J, Du Pont JS, Hoefsmit EC, Kamperdijk EW. Isolation and characterization of migratory human skin dendritic cells. Clin Exp Immunol. 1994 Nov;98(2):330–336. [PubMed]
  • Richters CD, Hoekstra MJ, Van Baare J, Du Pont JS, Hoefsmit EC, Kamperdijk EW. Migratory properties and functional capacities of human skin dendritic cells. Br J Dermatol. 1995 Nov;133(5):721–727. [PubMed]
  • Sornasse T, Flamand V, De Becker G, Bazin H, Tielemans F, Thielemans K, Urbain J, Leo O, Moser M. Antigen-pulsed dendritic cells can efficiently induce an antibody response in vivo. J Exp Med. 1992 Jan 1;175(1):15–21. [PMC free article] [PubMed]
  • Soto-Ramirez LE, Renjifo B, McLane MF, Marlink R, O'Hara C, Sutthent R, Wasi C, Vithayasai P, Vithayasai V, Apichartpiyakul C, et al. HIV-1 Langerhans' cell tropism associated with heterosexual transmission of HIV. Science. 1996 Mar 1;271(5253):1291–1293. [PubMed]
  • Spira AI, Marx PA, Patterson BK, Mahoney J, Koup RA, Wolinsky SM, Ho DD. Cellular targets of infection and route of viral dissemination after an intravaginal inoculation of simian immunodeficiency virus into rhesus macaques. J Exp Med. 1996 Jan 1;183(1):215–225. [PMC free article] [PubMed]
  • Steinman RM. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–296. [PubMed]
  • Subbarao S, Schochetman G. Genetic variability of HIV-1. AIDS. 1996;10 (Suppl A):S13–S23. [PubMed]
  • Trkola A, Dragic T, Arthos J, Binley JM, Olson WC, Allaway GP, Cheng-Mayer C, Robinson J, Maddon PJ, Moore JP. CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5. Nature. 1996 Nov 14;384(6605):184–187. [PubMed]
  • van Harmelen J, Wood R, Lambrick M, Rybicki EP, Williamson AL, Williamson C. An association between HIV-1 subtypes and mode of transmission in Cape Town, South Africa. AIDS. 1997 Jan;11(1):81–87. [PubMed]
  • Weissman D, Li Y, Ananworanich J, Zhou LJ, Adelsberger J, Tedder TF, Baseler M, Fauci AS. Three populations of cells with dendritic morphology exist in peripheral blood, only one of which is infectable with human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):826–830. [PubMed]
  • Weniger BG, Limpakarnjanarat K, Ungchusak K, Thanprasertsuk S, Choopanya K, Vanichseni S, Uneklabh T, Thongcharoen P, Wasi C. The epidemiology of HIV infection and AIDS in Thailand. AIDS. 1991;5 (Suppl 2):S71–S85. [PubMed]
  • Zhang L, Huang Y, He T, Cao Y, Ho DD. HIV-1 subtype and second-receptor use. Nature. 1996 Oct 31;383(6603):768–768. [PubMed]

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