1887

Journal of General Virology header logo

Volume 78, Issue 10

Syncytium formation induced by human immunodeficiency virus type 1 isolates correlates with affinity for CD4. Free

Abstract

Different strains of human immunodeficiency virus type 1 (HIV-1) show considerable divergence in genetic content and biological properties. One property that has been closely correlated with clinical prognosis is the ability to induce syncytia formation in susceptible cells. This ability had been correlated with the V3 loop sequence of major envelope glycoprotein, gp120, but recent reports have questioned this connection. We investigated the contributions of different regions of the gene to syncytia induction using chimeric viruses that contain part of the genome of a strain that lacks this ability (HIV-1) within the genome of a virus that can form syncytia (HIV-1). When tested in two cell lines susceptible to both parental viruses, as well as in primary cells, these chimeric viruses demonstrated that the ability to induce syncytia formation was determined by regions of env outside the V3 loop, which encompass residues that contribute to the binding of CD4 by gp120. Further investigation failed to show any difference in the expression of gp120 on the cell surface or cell adhesion molecules by cells infected with SI or NSI variants that would explain the observed differences in the ability to form syncytia. Assays of relative affinity for CD4 indicated that gp120 from SI variants showed a significantly higher affinity for CD4 than gp120 from NSI variants. These observations suggest that areas of the HIV-1 gene contributing to the CD4 binding site may also contribute to the determination of syncytium- inducing (SI) and non-syncytium-inducing (NSI) phenotypes.

  • Published Online:
© Society for General Microbiology 1997
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-78-10-2513
1997-10-01
2024-04-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/78/10/9349472.html?itemId=/content/journal/jgv/10.1099/0022-1317-78-10-2513&mimeType=html&fmt=ahah

References

  1. Andeweg A. C., Leeflang P., Osterhaus A. D., Bosch M. L. 1993; Both the V2 and V3 regions of the human immunodeficiency virus type 1 surface glycoprotein functionally interact with other envelope regions in syncytia formation. Journal of Virology 67:3232–3239
     [Google Scholar]
  2. Andeweg A. C., Boers P. H. M., Osterhaus A. D., Bosch M. L. 1995; Impact of natural sequence variation in the V2 region of the envelope protein of human immunodeficiency virus type 1 on syncytium induction: a mutational analysis. Journal of General Virology 76:1901–1907
     [Google Scholar]
  3. Åsjö B., Albert J., Karlsson B., Morfeldt-Månson L., Biberfeld G., Lidman K., Fenyo E. M. 1986; Replicative properties of human immunodeficiency virus from patients with varying severity of HIV infection. Lancet ii:660–662
     [Google Scholar]
  4. Bozzette S. A., McCutchen J. A., Spector S. A., Wright B., Richman D. D. 1993; A Cross-sectional analysis of persons with syncytium- and non-syncytium-inducing human immunodeficiency virus. Journal of Infectious Diseases 168:1374–1379
     [Google Scholar]
  5. Butini L., De Fougerolles A. R., Vaccarezza M., Graziosi C., Cohen D. I., Montroni M., Springer T. A., Pantaleo G., Fauci A. S. 1994; Intercellular adhesion molecules (ICAM)-1 ICAM-2 and ICAM-3 function as counter-receptors for lymphocyte function-associated molecule 1 in human immunodeficiency virus-mediated syncytia formation. European Journal of Immunology 24:2191–2195
     [Google Scholar]
  6. Cann A. J., Churcher M. J., Boyd M., O’Brien W., Zhao J.-Q., Zack J., Chen I. S. Y. 1992; The region of the envelope gene of human immunodeficiency virus type 1 responsible for determination of cell tropism. Journal of Virology 66:305–309
     [Google Scholar]
  7. Carrillo A., Trowbridge D. B., Westervelt P., Ratner L. 1993; Identification of HIV-1 determinants for T lymphoid cell line infection. Virology 197:817–824
     [Google Scholar]
  8. Chesebro B., Nishio J., Perryman S., Cann A., O’Brien W., Chen I. S. Y., Wherly K. 1991; Identification of human immunodeficiency virus envelope gene sequences influencing viral entry into CD4-positive HeLa cells, T-leukemia cells and macrophages. Journal of Virology 65:5782–5789
     [Google Scholar]
  9. Chesebro B., Wherly K., Nishio J., Perryman S. 1992; 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. Journal of Virology 66:6547–6554
     [Google Scholar]
  10. Choe H., Farzan M., Sun Y., Sullivan N., Rollins B., Ponath P. D., Wu L., Mackay C. R., Larosa G., Newman W., Gerard N., Gerard C., Sodroski J. 1996; The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 85:1135–1148
     [Google Scholar]
  11. Cornelissen M., Hogervorst E., Zorgdrager F., Hartman S., Goudsmit J. 1995; Maintenance of syncytium-inducing phenotype of HIV type 1 is associated with positively charged residues in the HIV type 1 gp120 V2 domain without fixed positions, elongation, or relocated N- linked glycosylation sites. AIDS Research and Human Retroviruses 11:1169–1175
     [Google Scholar]
  12. De Jong J.-J., De Ronde A., Keulen W., Tersmette M., Goudsmit J. 1992; Minimal requirements for the human immunodeficiency virus type 1 V3 domain to support the syncytium-inducing phenotype : analysis by single amino acid substitution. Journal of Virology 66:6777–6780
     [Google Scholar]
  13. Feng Y., Broder C. C., Kennedy P. E., Berger E. A. 1996; HIV-1 entry co-factor: functional cDNA cloning of a seven-transmembrane G protein-coupled receptor. Science 272:872–877
     [Google Scholar]
  14. Fisher A. G., Collati E., Ratner L., Gallo R. C., Wong-Staal F. 1985; A molecular clone of HTLV-III with biologic activity. Nature 316:262–265
     [Google Scholar]
  15. Forte S. E., Byron K. S., Sullivan J. L., Somasundaran M. 1994; Non-syncytium-inducing HIV type 1 isolated from infected individuals replicates in MT-2 cells. AIDS Research and Human Retroviruses 10:1613–1618
     [Google Scholar]
  16. Fouchier R. A. M., Brouwer M., Broersen S. M., Schuitemaker H. 1995; Simple determination of human immunodeficiency virus type 1 syncytium-inducing V3 genotype by PCR. Journal of Clinical Microbiology 33:906–911
     [Google Scholar]
  17. Fouchier R. A. M., Meynaard L., Brouwer M., Hovenkamp E., Schuitemaker H. 1996; Broader tropism and higher cytopathicity for CD4+ T-cells of a syncytium-inducing compared to a non-syncytium- inducing HIV-1 isolate as a mechanism for accelerated CD4+ T cell decline in vivo. Virology 219:87–95
     [Google Scholar]
  18. Fu Y.-K., Hart T. K., Jonak Z. L., Bugelski P. J. 1993; Physicochemical dissociation of CD4-mediated syncytium formation and shedding of human immunodeficiency virus type 1 gp120. Journal of Virology 67:3818–3825
     [Google Scholar]
  19. Gartner S., Markovits P., Markovitz D. M., Kaplan M. H., Gallo R. C., Popovic M. 1986; The role of mononuclear phagocytes in HTLV- III LAV infection. Science 233:215–219
     [Google Scholar]
  20. Groenink M., Andeweg A. C., Fouchier R. A. M., Broersen S., Van der Jagt R. C. M., Schuitemaker H., De Goede R. E. Y., Bosch M. L., Huisman H. G., Tersmette M. 1992; 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. Journal of Virology 66:6175–6180
     [Google Scholar]
  21. Harrowe G., Cheng-Meyer C. 1995; Amino acid substitutions in the V3 loop are responsible for adaptation to growth in transformed T-cell lines of a primary human immunodeficiency virus type 1. Virology 210:490–494
     [Google Scholar]
  22. Hwang S. S., Boyle T. J., Lyerly H. K., Cullen B. R. 1991; Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1. Science 253:71–74
     [Google Scholar]
  23. Holm-Hansen C., Grothues D., Rustad S., Røsok B., Rodica-Pascu F., Åsjö B. 1995; Characterization of HIV type 1 from Romanian children: lack of correlation between V3 loop amino acid sequence and syncytium formation in MT-2 cells. AIDS Research and Human Retroviruses 11:597–603
     [Google Scholar]
  24. Kuiken C. L., DeJong J.-J., Baan E., Keulen W., Tersmette M., Goudsmit J. 1992; Evolution of the V3 envelope domain in proviral sequences and isolates of human immunodeficiency virus type 1 during transition of the viral biological phenotype. Journal of Virology 66:4622–7
     [Google Scholar]
  25. Kozak S. L., Platt E. J., Mandani N., Ferro F. E.Jr Peden K., Kabat D. 1997; CCR-5 dependencies for infections by primary patient and laboratory-adapted isolates of human immunodeficiency virus type 1. Journal of Virology 71:873–882
     [Google Scholar]
  26. Laskey L. A., Nakamura G., Smith D. H., Fennie C., Shimasaki C., Patzer E., Berman P., Gregory T., Capon D. J. 1987; Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell 50:975–985
     [Google Scholar]
  27. Lusso P., Cocchi F., Balotta C., Markham P. D., Louie A., Farci P., Pal R., Gallo R. C., Reitz M. S.Jr 1995; Growth of macrophage- tropic and primary human immunodeficiency virus type 1 (HIV-1) isolates in a unique CD4+ T-cell clone (PM1): failure to down regulate CD4 and to interfere with cell-line-tropic HIV-1. Journal of Virology 69:3712–20
     [Google Scholar]
  28. Malykh A., Reitz M. S.Jr Louie A., Hall L., Lori F. 1995; Multiple determinants for growth of human immunodeficiency virus type 1 in monocyte-macrophages. Virology 206:646–50
     [Google Scholar]
  29. Moore J. P., Thali M., Jameson B. A., Vignaux F., Lewis G. K., Poon S.-W., Charles M., Fung M. S., Sun B., Durda P. J., Akerblom L., Wahren B., Ho D. D., Sattentau Q. J., Sodroski J. 1993; Immunochemical analysis of the gp120 surface glycoprotein of human immunodeficiency virus type 1 : probing the structure of the C4 and V4 domains and the interaction of with the V3 loop. Journal of Virology 67:4785–4796
     [Google Scholar]
  30. O’Brien W. A., Koyanagi Y., Namazie A., Zhao J. Q., Diagne A., Idler K., Zack J. A., Chen I. S. Y. 1990; HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domain. Nature 348:69–73
     [Google Scholar]
  31. Olshevsky U., Helseth E., Furman C., Li J., Haseltine W., Sodroski J. 1990; Identification of individual human immunodeficiency virus type 1 gp120 amino acids important for CD4 receptor binding. Journal of Virology 64:5701–5707
     [Google Scholar]
  32. Pinter A., Honnen W. J., Tilley S. A. 1993; Conformational changes affecting the V3 and CD4-binding domains of human immunodeficiency virus type 1 gp120 associated with env processing and binding of ligand to these sites. Journal of Virology 67:5692–5697
     [Google Scholar]
  33. Platt E. J., Madani N., Kozak S. L., Kabat D. 1997; Infectious properties of human immunodeficiency virus type 1 mutants with distinct affinities for the CD4 receptor. Journal of Virology 71:883–890
     [Google Scholar]
  34. Richman D. D., Bozzette S. A. 1994; The impact of the syncytium- inducing phenotype of human immunodeficiency virus on disease progression. Journal of Infectious Diseases 169:968–974
     [Google Scholar]
  35. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: A Laboratory Manual, 2nd edn.. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
     [Google Scholar]
  36. Schuitemaker H., Kootstra N. A., De Goede R. E. Y., De Wolf F., Miedema F., Tersmette M. 1991; 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. Journal of Virology 65:356–363
     [Google Scholar]
  37. Shoida T., Levy J. A., Cheng-Mayer C. 1991; Macrophage and T cell-line tropisms are determined by specific regions of the envelope gp120 gene. Nature 349:167–169
     [Google Scholar]
  38. Sullivan N., Thali M., Furman C., Ho D. D., Sodroski J.F. 1993; Effect of amino acid changes in the V1/V2 region of the human immunodeficiency virus type 1 gp120 glycoprotein on subunit association, syncytium formation, and recognition by a neutralizing antibody. Journal of Virology 67:3674–3679
     [Google Scholar]
  39. Todd B. J., Kedar P., Pope J. H. 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. Journal of Virology 69:7099–7105
     [Google Scholar]
  40. Veronese F. D., Reitz M. S.Jr Gupta G., Robert-Guroff M., Boyer-Thompson C., Louie A. T., Gallo R. C., P. Lusso P. 1993; Loss of a neutralizing epitope by a spontaneous point mutation in the V3 loop of HIV-1 isolated from an infected laboratory worker. Journal of Biological Chemistry 268:25894–25901
     [Google Scholar]
  41. Watkins B. A., Reitz M. S.Jr 1996; Using the polymerase chain reaction for rapid site-specific mutagenesis in large plasmids. Methods in Molecular Biology 57:217–227
     [Google Scholar]
  42. Watkins B. A., Dorn H. H., Kelly W. B., Armstrong R. C., Potts B. J., Micheals F., Kufta C. V., Dubois-Dalcq M. 1990; Specific tropism of HIV-1 for microglial cells in primary human brain cultures. Science 249:549–553
     [Google Scholar]
  43. Watkins B. A., Reitz M. S., Wilson C. A., Aldrich K., Davis A. E., Robert-Guroff M. 1993; Immune escape by human immunodeficiency virus type-1 from neutralizing antibodies : evidence for multiple pathways. Journal of Virology 67:7493–7500
     [Google Scholar]
  44. Watkins B. A., Davis A. E., Fiorentini S., Reitz M. S.Jr 1995; V-region and class specific RT-PCR amplification ofhuman immunoglobulin heavy and light chain genes from B-cell lines. Scandinavian Journal of Immunology 42:442–448
     [Google Scholar]
  45. Watkins B. A., Crowley R. W., Davis A. E., Louie A. T., Reitz M. S.Jr 1996a; Expression of CD26 does not correlate with the replication of macrophage-tropic strains of HIV-1 in T-cell lines. Virology 224:276–280
     [Google Scholar]
  46. Watkins B. A., Davis A. E., Fiorentini S., Veronese F. D., Reitz M. S.Jr 1996b; Evidence for distinct contributions of heavy and light chains to antibody recognition of the human immunodeficiency virus type-1 principal neutralization determinant. Journal of Immunology 156:1676–1683
     [Google Scholar]
  47. Wyatt R., Thali M., Tilley S., Pinter A., Posner M., Ho D., Robinson J., Sodroski J. 1992; Relationship of the human immunodeficiency virus type 1 gp120 third variable loop to a component of the CD4 binding site in the forth conserved region. Journal of Virology 66:6997–7004
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-78-10-2513
Loading
Syncytium formation induced by human immunodeficiency virus type 1 isolates correlates with affinity for CD4.
J. Gen. Virol. 78, 2513 (1997); https://doi.org/10.1099/0022-1317-78-10-2513
/content/journal/jgv/10.1099/0022-1317-78-10-2513
/content/journal/jgv/10.1099/0022-1317-78-10-2513
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error