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. 1995 Nov;69(11):7099–7105. doi: 10.1128/jvi.69.11.7099-7105.1995

Syncytium induction in primary CD4+ T-cell lines from normal donors by human immunodeficiency virus type 1 isolates with non-syncytium-inducing genotype and phenotype in MT-2 cells.

B J Todd 1, P Kedar 1, J H Pope 1
PMCID: PMC189629  PMID: 7474129

Abstract

Human immunodeficiency virus type 1 (HIV-1) isolates classified as syncytium-inducing (SI) or non-SI (NSI) in the MT-2 T-cell line exhibit characteristic sequence differences in the V1-V2 and V3 regions of the env gene. Seven HIV-1 isolates were phenotyped as NSI or SI in the MT-2 cell line. Unexpectedly, all four NSI viruses induced large syncytia 4 to 8 days postinoculation in a panel of five primary CD4+ T-cell lines (including two clones) generated from the peripheral blood of normal donors by exposure to infectious HIV-1, inactivated HIV-1, or Epstein-Barr virus. The primary T-cell lines yielded neither HIV-1 provirus nor infectious HIV by PCR analysis or exhaustive coculture with phytohemagglutinin-treated blast cells. Three isolates (TC354, PK1, and PK2) were biologically cloned and retained their SI or NSI phenotypes in MT-2 and primary T-cell lines. The biologically cloned provirus DNA was also used to clone and sequence the relevant V2 and V3 regions of the env genes. The amino acid sequences of the V2 and V3 regions were characteristic of patterns already reported for the NSI, switch NSI, and SI phenotypes, respectively. This evidence precludes the possibility that these results were due to contamination of the NSI isolates with SI virus. The results unequivocally indicate that HIV-1 isolates with the NSI genotype and phenotype in MT-2 cells may actively induce syncytia in cloned CD4+ T cells in vitro and support the view that direct cytopathic effects may contribute to the steady decline in CD4+ T cells in asymptomatic HIV-1-seropositive patients without detectable SI virus.

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Selected References

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  1. Aldrovandi G. M., Feuer G., Gao L., Jamieson B., Kristeva M., Chen I. S., Zack J. A. The SCID-hu mouse as a model for HIV-1 infection. Nature. 1993 Jun 24;363(6431):732–736. doi: 10.1038/363732a0. [DOI] [PubMed] [Google Scholar]
  2. Asjö B., Morfeldt-Månson L., Albert J., Biberfeld G., Karlsson A., Lidman K., Fenyö E. M. Replicative capacity of human immunodeficiency virus from patients with varying severity of HIV infection. Lancet. 1986 Sep 20;2(8508):660–662. [PubMed] [Google Scholar]
  3. Cheng-Mayer C., Shioda T., Levy J. A. Host range, replicative, and cytopathic properties of human immunodeficiency virus type 1 are determined by very few amino acid changes in tat and gp120. J Virol. 1991 Dec;65(12):6931–6941. doi: 10.1128/jvi.65.12.6931-6941.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Daar E. S., Chernyavskiy T., Zhao J. Q., Krogstad P., Chen I. S., Zack J. A. Sequential determination of viral load and phenotype in human immunodeficiency virus type 1 infection. AIDS Res Hum Retroviruses. 1995 Jan;11(1):3–9. doi: 10.1089/aid.1995.11.3. [DOI] [PubMed] [Google Scholar]
  5. Donaldson Y. K., Bell J. E., Holmes E. C., Hughes E. S., Brown H. K., Simmonds P. In vivo distribution and cytopathology of variants of human immunodeficiency virus type 1 showing restricted sequence variability in the V3 loop. J Virol. 1994 Sep;68(9):5991–6005. doi: 10.1128/jvi.68.9.5991-6005.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fouchier R. A., Groenink M., Kootstra N. A., Tersmette M., Huisman H. G., 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. doi: 10.1128/jvi.66.5.3183-3187.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Groenink M., Fouchier R. A., Broersen S., Baker C. H., Koot M., van't Wout A. B., Huisman H. G., Miedema F., Tersmette M., Schuitemaker H. Relation of phenotype evolution of HIV-1 to envelope V2 configuration. Science. 1993 Jun 4;260(5113):1513–1516. doi: 10.1126/science.8502996. [DOI] [PubMed] [Google Scholar]
  8. Haertle T., Carrera C. J., Wasson D. B., Sowers L. C., Richman D. D., Carson D. A. Metabolism and anti-human immunodeficiency virus-1 activity of 2-halo-2',3'-dideoxyadenosine derivatives. J Biol Chem. 1988 Apr 25;263(12):5870–5875. [PubMed] [Google Scholar]
  9. Harada S., Koyanagi Y., Yamamoto N. Infection of HTLV-III/LAV in HTLV-I-carrying cells MT-2 and MT-4 and application in a plaque assay. Science. 1985 Aug 9;229(4713):563–566. doi: 10.1126/science.2992081. [DOI] [PubMed] [Google Scholar]
  10. Ho D. D., Neumann A. U., Perelson A. S., Chen W., Leonard J. M., Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995 Jan 12;373(6510):123–126. doi: 10.1038/373123a0. [DOI] [PubMed] [Google Scholar]
  11. Kollmann T. R., Kim A., Pettoello-Mantovani M., Hachamovitch M., Rubinstein A., Goldstein M. M., Goldstein H. Divergent effects of chronic HIV-1 infection on human thymocyte maturation in SCID-hu mice. J Immunol. 1995 Jan 15;154(2):907–921. [PubMed] [Google Scholar]
  12. Koot M., Keet I. P., Vos A. H., de Goede R. E., Roos M. T., Coutinho R. A., Miedema F., Schellekens P. T., 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. doi: 10.7326/0003-4819-118-9-199305010-00004. [DOI] [PubMed] [Google Scholar]
  13. Koot M., Vos A. H., Keet R. P., de Goede R. E., Dercksen M. W., Terpstra F. G., Coutinho R. A., Miedema F., Tersmette M. HIV-1 biological phenotype in long-term infected individuals evaluated with an MT-2 cocultivation assay. AIDS. 1992 Jan;6(1):49–54. doi: 10.1097/00002030-199201000-00006. [DOI] [PubMed] [Google Scholar]
  14. Levy J. A. Pathogenesis of human immunodeficiency virus infection. Microbiol Rev. 1993 Mar;57(1):183–289. doi: 10.1128/mr.57.1.183-289.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Misko I. S., Pope J. H., Hütter R., Soszynski T. D., Kane R. G. HLA-DR-antigen-associated restriction of EBV-specific cytotoxic T-cell colonies. Int J Cancer. 1984 Feb 15;33(2):239–243. doi: 10.1002/ijc.2910330212. [DOI] [PubMed] [Google Scholar]
  16. Mosier D. E., Gulizia R. J., MacIsaac P. D., Torbett B. E., Levy J. A. Rapid loss of CD4+ T cells in human-PBL-SCID mice by noncytopathic HIV isolates. Science. 1993 Apr 30;260(5108):689–692. doi: 10.1126/science.8097595. [DOI] [PubMed] [Google Scholar]
  17. Nielsen C., Pedersen C., Lundgren J. D., 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. doi: 10.1097/00002030-199308000-00002. [DOI] [PubMed] [Google Scholar]
  18. Pantaleo G., Graziosi C., Fauci A. S. New concepts in the immunopathogenesis of human immunodeficiency virus infection. N Engl J Med. 1993 Feb 4;328(5):327–335. doi: 10.1056/NEJM199302043280508. [DOI] [PubMed] [Google Scholar]
  19. Pope J. H., Bisshop F., McRandle B., Blok J., Schmidt C. W., Kemp R. J. The value of MLA 144 culture fluid for the isolation of human immunodeficiency virus. Immunol Cell Biol. 1989 Apr;67(Pt 2):147–149. doi: 10.1038/icb.1989.21. [DOI] [PubMed] [Google Scholar]
  20. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  21. Richman D. D., Bozzette S. A. The impact of the syncytium-inducing phenotype of human immunodeficiency virus on disease progression. J Infect Dis. 1994 May;169(5):968–974. doi: 10.1093/infdis/169.5.968. [DOI] [PubMed] [Google Scholar]
  22. Schuitemaker H., Koot M., Kootstra N. A., Dercksen M. W., de Goede R. E., van Steenwijk R. P., Lange J. M., Schattenkerk J. K., 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. doi: 10.1128/jvi.66.3.1354-1360.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shimizu H., Hasebe F., Tsuchie H., Morikawa S., Ushijima H., Kitamura T. Analysis of a human immunodeficiency virus type 1 isolate carrying a truncated transmembrane glycoprotein. Virology. 1992 Aug;189(2):534–546. doi: 10.1016/0042-6822(92)90577-c. [DOI] [PubMed] [Google Scholar]
  24. Simmonds P., Balfe P., Peutherer J. F., Ludlam C. A., Bishop J. O., Brown A. J. Human immunodeficiency virus-infected individuals contain provirus in small numbers of peripheral mononuclear cells and at low copy numbers. J Virol. 1990 Feb;64(2):864–872. doi: 10.1128/jvi.64.2.864-872.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Todd B., Pope J. H., Georghiou P. Interleukin-2 enhances production in 24 hours of infectious human immunodeficiency virus type 1 in vitro by naturally infected mononuclear cells from seropositive donors. Arch Virol. 1991;121(1-4):227–232. doi: 10.1007/BF01316757. [DOI] [PubMed] [Google Scholar]
  26. Wang N., Zhu T., Ho D. D. Sequence diversity of V1 and V2 domains of gp120 from human immunodeficiency virus type 1: lack of correlation with viral phenotype. J Virol. 1995 Apr;69(4):2708–2715. doi: 10.1128/jvi.69.4.2708-2715.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wei X., Ghosh S. K., Taylor M. E., Johnson V. A., Emini E. A., Deutsch P., Lifson J. D., Bonhoeffer S., Nowak M. A., Hahn B. H. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995 Jan 12;373(6510):117–122. doi: 10.1038/373117a0. [DOI] [PubMed] [Google Scholar]
  28. Weiss R. A. How does HIV cause AIDS? Science. 1993 May 28;260(5112):1273–1279. doi: 10.1126/science.8493571. [DOI] [PubMed] [Google Scholar]
  29. Zack J. A., Arrigo S. J., Weitsman S. R., Go A. S., Haislip A., Chen I. S. HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell. 1990 Apr 20;61(2):213–222. doi: 10.1016/0092-8674(90)90802-l. [DOI] [PubMed] [Google Scholar]
  30. Zhu T., Mo H., Wang N., Nam D. S., Cao Y., Koup R. A., Ho D. D. Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science. 1993 Aug 27;261(5125):1179–1181. doi: 10.1126/science.8356453. [DOI] [PubMed] [Google Scholar]
  31. Zinkernagel R. M., Hengartner H. T-cell-mediated immunopathology versus direct cytolysis by virus: implications for HIV and AIDS. Immunol Today. 1994 Jun;15(6):262–268. doi: 10.1016/0167-5699(94)90005-1. [DOI] [PubMed] [Google Scholar]

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