Search tips
Search criteria 


Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. 1994 November; 94(5): 2060–2067.
PMCID: PMC294642

Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual, parenteral, and vertical transmission.


Macrophage-tropic, non-syncytium-inducing, HIV-1 variants predominate in the asymptomatic phase of infection and may be responsible for establishing infection in an individual exposed to the mixture of HIV-1 variants. Here, genotypical and phenotypical characteristics of virus populations, present in sexual, parenteral, or vertical donor-recipient pairs, were studied. Sequence analysis of the V3 domain confirmed the presence of a homogeneous virus population in recently infected individuals. Biological HIV-1 clones were further characterized for syncytium inducing capacity on the MT2 cell line and for macrophage tropism as defined by the appearance of proviral DNA upon inoculation of monocyte-derived macrophages. Both sexual and parenteral transmission cases revealed a selective outgrowth in the recipient of the most macrophage-tropic variant(s) present in the donor. In three out of five vertical transmission cases, more than one highly macrophage-tropic virus variant was present in the child shortly after birth, suggestive of transmission of multiple variants. In three primary infection cases, homogeneous virus populations of macrophage-tropic, non-syncytium-inducing variants were present prior to seroconversion, thus excluding humoral immunity as the selective pressure in favour of macrophage-tropic variants. These observations may have important implications for vaccine development.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Asjö B, Morfeldt-Månson L, Albert J, Biberfeld G, Karlsson A, Lidman K, Fenyö EM. Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection. Lancet. 1986 Sep 20;2(8508):660–662. [PubMed]
  • von Briesen H, Becker WB, Henco K, Helm EB, Gelderblom HR, Brede HD, Rübsamen-Waigmann H. Isolation frequency and growth properties of HIV-variants: multiple simultaneous variants in a patient demonstrated by molecular cloning. J Med Virol. 1987 Sep;23(1):51–66. [PubMed]
  • Evans LA, McHugh TM, Stites DP, Levy JA. Differential ability of human immunodeficiency virus isolates to productively infect human cells. J Immunol. 1987 May 15;138(10):3415–3418. [PubMed]
  • Cheng-Mayer C, Seto D, Tateno M, Levy JA. Biologic features of HIV-1 that correlate with virulence in the host. Science. 1988 Apr 1;240(4848):80–82. [PubMed]
  • Tersmette M, de Goede RE, Al BJ, Winkel IN, Gruters RA, Cuypers HT, Huisman HG, Miedema F. Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. J Virol. 1988 Jun;62(6):2026–2032. [PMC free article] [PubMed]
  • Koot M, Keet IP, Vos AH, de Goede RE, Roos MT, Coutinho RA, Miedema F, Schellekens PT, Tersmette M. Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med. 1993 May 1;118(9):681–688. [PubMed]
  • Schuitemaker H, Kootstra NA, de Goede RE, de Wolf F, Miedema F, Tersmette M. Monocytotropic human immunodeficiency virus type 1 (HIV-1) variants detectable in all stages of HIV-1 infection lack T-cell line tropism and syncytium-inducing ability in primary T-cell culture. J Virol. 1991 Jan;65(1):356–363. [PMC free article] [PubMed]
  • Schuitemaker H, Koot M, Kootstra NA, Dercksen MW, de Goede RE, van Steenwijk RP, Lange JM, Schattenkerk JK, Miedema F, Tersmette M. Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population. J Virol. 1992 Mar;66(3):1354–1360. [PMC free article] [PubMed]
  • Keet IP, Krijnen P, Koot M, Lange JM, Miedema F, Goudsmit J, Coutinho RA. Predictors of rapid progression to AIDS in HIV-1 seroconverters. AIDS. 1993 Jan;7(1):51–57. [PubMed]
  • Groenink M, Fouchier RA, de Goede RE, de Wolf F, Gruters RA, Cuypers HT, Huisman HG, Tersmette M. Phenotypic heterogeneity in a panel of infectious molecular human immunodeficiency virus type 1 clones derived from a single individual. J Virol. 1991 Apr;65(4):1968–1975. [PMC free article] [PubMed]
  • Roos MT, Lange JM, de Goede RE, Coutinho RA, Schellekens PT, Miedema F, Tersmette M. Viral phenotype and immune response in primary human immunodeficiency virus type 1 infection. J Infect Dis. 1992 Mar;165(3):427–432. [PubMed]
  • Baur A, Schwarz N, Ellinger S, Korn K, Harrer T, Mang K, Jahn G. Continuous clearance of HIV in a vertically infected child. Lancet. 1989 Oct 28;2(8670):1045–1045. [PubMed]
  • de Jong JJ, Goudsmit J, Keulen W, Klaver B, Krone W, Tersmette M, de Ronde A. Human immunodeficiency virus type 1 clones chimeric for the envelope V3 domain differ in syncytium formation and replication capacity. J Virol. 1992 Feb;66(2):757–765. [PMC free article] [PubMed]
  • Fouchier RA, Groenink M, Kootstra NA, Tersmette M, Huisman HG, Miedema F, Schuitemaker H. Phenotype-associated sequence variation in the third variable domain of the human immunodeficiency virus type 1 gp120 molecule. J Virol. 1992 May;66(5):3183–3187. [PMC free article] [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]
  • Zhang LQ, MacKenzie P, Cleland A, Holmes EC, Brown AJ, Simmonds P. Selection for specific sequences in the external envelope protein of human immunodeficiency virus type 1 upon primary infection. J Virol. 1993 Jun;67(6):3345–3356. [PMC free article] [PubMed]
  • McNearney T, Hornickova Z, Markham R, Birdwell A, Arens M, Saah A, Ratner L. Relationship of human immunodeficiency virus type 1 sequence heterogeneity to stage of disease. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10247–10251. [PubMed]
  • Kuiken CL, Zwart G, Baan E, Coutinho RA, van den Hoek JA, Goudsmit J. Increasing antigenic and genetic diversity of the V3 variable domain of the human immunodeficiency virus envelope protein in the course of the AIDS epidemic. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9061–9065. [PubMed]
  • Zhu T, Mo H, Wang N, Nam DS, Cao Y, Koup RA, Ho DD. Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science. 1993 Aug 27;261(5125):1179–1181. [PubMed]
  • Lange JM, Boucher CA, Hollak CE, Wiltink EH, Reiss P, van Royen EA, Roos M, Danner SA, Goudsmit J. Failure of zidovudine prophylaxis after accidental exposure to HIV-1. N Engl J Med. 1990 May 10;322(19):1375–1377. [PubMed]
  • Boom R, Sol CJ, Salimans MM, Jansen CL, Wertheim-van Dillen PM, van der Noordaa J. Rapid and simple method for purification of nucleic acids. J Clin Microbiol. 1990 Mar;28(3):495–503. [PMC free article] [PubMed]
  • Simmonds P, Balfe P, Ludlam CA, Bishop JO, Brown AJ. Analysis of sequence diversity in hypervariable regions of the external glycoprotein of human immunodeficiency virus type 1. J Virol. 1990 Dec;64(12):5840–5850. [PMC free article] [PubMed]
  • Fouchier RA, Brouwer M, Kootstra NA, Huisman HG, Schuitemaker H. HIV-1 macrophage tropism is determined at multiple levels of the viral replication cycle. J Clin Invest. 1994 Nov;94(5):1806–1814. [PMC free article] [PubMed]
  • Schuitemaker H, Groenink M, Meyaard L, Kootstra NA, Fouchier RA, Gruters RA, Huisman HG, Tersmette M, Miedema F. Early replication steps but not cell type-specific signalling of the viral long terminal repeat determine HIV-1 monocytotropism. AIDS Res Hum Retroviruses. 1993 Jul;9(7):669–675. [PubMed]
  • O'Brien WA, Koyanagi Y, Namazie A, Zhao JQ, Diagne A, Idler K, Zack JA, Chen IS. HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domain. Nature. 1990 Nov 1;348(6296):69–73. [PubMed]
  • Shioda T, Levy JA, Cheng-Mayer C. Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions of the envelope gp120 gene. Nature. 1991 Jan 10;349(6305):167–169. [PubMed]
  • Bruisten SM, Koppelman MH, van der Poel CL, Huisman JG. Enhanced detection of HIV-1 sequences using polymerase chain reaction and a liquid hybridization technique. Application for individuals with questionable HIV-1 infection. Vox Sang. 1991;61(1):24–29. [PubMed]
  • Mulder-Kampinga GA, Kuiken C, Dekker J, Scherpbier HJ, Boer K, Goudsmit J. Genomic human immunodeficiency virus type 1 RNA variation in mother and child following intra-uterine virus transmission. J Gen Virol. 1993 Sep;74(Pt 9):1747–1756. [PubMed]
  • Clark SJ, Saag MS, Decker WD, Campbell-Hill S, Roberson JL, Veldkamp PJ, Kappes JC, Hahn BH, Shaw GM. High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. N Engl J Med. 1991 Apr 4;324(14):954–960. [PubMed]
  • Nielsen C, Pedersen C, Lundgren JD, Gerstoft J. Biological properties of HIV isolates in primary HIV infection: consequences for the subsequent course of infection. AIDS. 1993 Aug;7(8):1035–1040. [PubMed]
  • Wolfs TF, Zwart G, Bakker M, Goudsmit J. HIV-1 genomic RNA diversification following sexual and parenteral virus transmission. Virology. 1992 Jul;189(1):103–110. [PubMed]
  • Scarlatti G, Leitner T, Halapi E, Wahlberg J, Marchisio P, Clerici-Schoeller MA, Wigzell H, Fenyö EM, Albert J, Uhlén M, et al. Comparison of variable region 3 sequences of human immunodeficiency virus type 1 from infected children with the RNA and DNA sequences of the virus populations of their mothers. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1721–1725. [PubMed]
  • Lamers SL, Sleasman JW, She JX, Barrie KA, Pomeroy SM, Barrett DJ, Goodenow MM. Persistence of multiple maternal genotypes of human immunodeficiency virus type I in infants infected by vertical transmission. J Clin Invest. 1994 Jan;93(1):380–390. [PMC free article] [PubMed]
  • McNearney T, Westervelt P, Thielan BJ, Trowbridge DB, Garcia J, Whittier R, Ratner L. Limited sequence heterogeneity among biologically distinct human immunodeficiency virus type 1 isolates from individuals involved in a clustered infectious outbreak. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1917–1921. [PubMed]
  • Groenink M, Andeweg AC, Fouchier RA, Broersen S, van der Jagt RC, Schuitemaker H, de Goede RE, Bosch ML, Huisman HG, Tersmette M. Phenotype-associated env gene variation among eight related human immunodeficiency virus type 1 clones: evidence for in vivo recombination and determinants of cytotropism outside the V3 domain. J Virol. 1992 Oct;66(10):6175–6180. [PMC free article] [PubMed]
  • Westervelt P, Gendelman HE, Ratner L. Identification of a determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3097–3101. [PubMed]
  • Simmonds P, Zhang LQ, McOmish F, Balfe P, Ludlam CA, Brown AJ. Discontinuous sequence change of human immunodeficiency virus (HIV) type 1 env sequences in plasma viral and lymphocyte-associated proviral populations in vivo: implications for models of HIV pathogenesis. J Virol. 1991 Nov;65(11):6266–6276. [PMC free article] [PubMed]
  • Epstein LG, Kuiken C, Blumberg BM, Hartman S, Sharer LR, Clement M, Goudsmit J. HIV-1 V3 domain variation in brain and spleen of children with AIDS: tissue-specific evolution within host-determined quasispecies. Virology. 1991 Feb;180(2):583–590. [PubMed]
  • Braathen LR, Ramirez G, Kunze RO, Gelderblom H. Langerhans cells as primary target cells for HIV infection. Lancet. 1987 Nov 7;2(8567):1094–1094. [PubMed]
  • Massari FE, Poli G, Schnittman SM, Psallidopoulos MC, Davey V, Fauci AS. In vivo T lymphocyte origin of macrophage-tropic strains of HIV. Role of monocytes during in vitro isolation and in vivo infection. J Immunol. 1990 Jun 15;144(12):4628–4632. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation