Molecular Determinants of the V3 Loop of Human Immunodeficiency Virus Type 1 Glycoprotein gp120 Responsible for Controlling Cell Tropism Free

Abstract

We and others have identified the major determinant of cell tropism in human immunodeficiency virus type 1 (HIV-1) as the V3 loop of glycoprotein gpl20. We have conducted a detailed study of two molecularly cloned isolates of HIV-1, HIV and HIV, that differ in their tropism for immortalized CD4 cell lines, by constructing a series of site-directed mutations within the V3 loop of HIV based on the sequence of HIV. The phenotypes of these mutants fall into two classes, those which are viable and those which are not. A spontaneous mutant with significantly altered growth properties was also recovered and found to have an additional single amino acid change in the V3 loop sequence. The carboxy-terminal -strand part of the V3 loop is the major determinant of cell tropism. However, the results presented here indicate that the functional role of the V3 loop sequences can only be interpreted properly in the context of the original gpl20 backbone from which they were derived. These findings show that over-simplistic interpretation of sequence data derived from unknown mixtures of HIV variants in infected persons may be highly misleading.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-75-11-3249
1994-11-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/75/11/JV0750113249.html?itemId=/content/journal/jgv/10.1099/0022-1317-75-11-3249&mimeType=html&fmt=ahah

References

  1. Adachi A., Gendelman H. E., Koenig S., Folks T., Willey R., Rabson A., Martin M. A. 1986; Production of acquired immunodeficiency syndrome-associated retrovirus in human and non-human cells transfected with an infectious molecular clone. Journal of Virology 59:284–291
    [Google Scholar]
  2. Ball J. K., Holmes E. C., Whitwell H., Desselberger U. 1994; Genomic variation of human immunodeficiency virus type 1 HIV-1: molecular analyses of HIV-1 in sequential blood samples and various organs obtained at autopsy. Journal of General Virology 75:867–879
    [Google Scholar]
  3. Boyd M. T., Simpson G. R., Cann A. J., Johnson M. A., Weiss R. A. 1993; A single amino acid substitution in the Vl-loop of HIV-1JR-CSF alters cellular tropism. Journal of Virology 67:3649–3652
    [Google Scholar]
  4. Cann A. J. 1990; Stable and safe HIV provirus clones. Nucleic Acids Research 18:6153–6154
    [Google Scholar]
  5. Cann A. J., Zack J. A., Go A. S., Arrigo S. A., Koyanagi Y., Green P. L., Koyanagi Y., Pang S., Chen I. S. Y. 1990; Human immunodeficiency virus type 1 T-cell tropism is determined by events prior to provirus formation. Journal of Virology 64:4735–4742
    [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. Cheng-Mayer C., Quiroga M., Tung J. W., Dina D., Levy J. A. 1990; Viral determinants of human immunodeficiency virus type-1 T-cell or macrophage tropism, cytopathogenicity, and CD4 antigen modulation. Journal of Virology 64:4390–4398
    [Google Scholar]
  8. Chesebro B., Nishio J., Perryman S., Cann A. J., O’Brien W., Chen I. S. Y., Wehrly K. 1991; Identification of HIV envelope gene sequences influencing viral entry into CD4-positive HeLa cells, T leukaemia cells and macrophages. Journal of Virology 65:5782–5789
    [Google Scholar]
  9. Cordonnier A., Montagnier L., Emerman M. 1989; Single amino acid changes in HIV envelope affect viral tropism and receptor binding. Nature; London: 340571–574
    [Google Scholar]
  10. De Jong J., Goudsmit J., Keulen W., Klaver B., Krone W., Tersmette M., De Ronde A. 1992; Human immunodeficiency virus type 1 clones chimeric for the envelope V3 differ in syncytium formation and replication capacity. Journal of Virology 66:757–765
    [Google Scholar]
  11. Fouchier R. A. M., Groenink M., Kootstra N. A., Tersmette M., Huisman H. G., Miedema F., Schuitemaker H. 1992; Phenotype associated sequence variation in the third variable domain of the human immunodeficiency virus type 1 gpl20 molecule. Journal of Virology 66:3183–3187
    [Google Scholar]
  12. Freed E. O., Myers D. J., Risser R. 1991; Identification of the principal neutralisation determinant of human immunodeficiency virus type 1 as a fusion domain. Journal of Virology 65:190–194
    [Google Scholar]
  13. Ghiara J. B., Stura E. A., Stanfield R. L., Profy A. T., Wilson I. A. 1994; Crystal structure of the principal neutralization site of HIV-1. Science 264:82–85
    [Google Scholar]
  14. Grimalia R. J., Fuller B. A., Rennert P. D., Nelson M. B., Hammarskjöld M. L., Potts B., Murray M., Putney S. D., Gray G. 1992; Mutations in the principal neutralization de-terminant of HIV-1 affect syncytium formation, virus infectivity, growth kinetics and neutralization. Journal of Virology 66:1875–1883
    [Google Scholar]
  15. Helseth E., Kowalski M., Gabuzda D., Olshevsky U., Haseltine W., Sodroski J. 1990; Rapid complementation assays measuring replicative potential of human immunodeficiency virus type 1 envelope glycoprotein mutants. Journal of Virology 64:2416–2420
    [Google Scholar]
  16. Hwang S. S., Boyle T. J., Lyerly H. K., Culen 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]
  17. Hwang S. S., Boyle T. J., Lyerly H. K., Culen B. R. 1992; Identification of envelope V3 loop as the major determinant of CD4 neutralisation sensitivity of HIV-1. Science 257:535–536
    [Google Scholar]
  18. Koyanagi Y., Miles S., Mitsuyasu R. T., Merrill J. E., Vintners H. V., Chen I. S. Y. 1987; Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science 236:819–822
    [Google Scholar]
  19. Liu Z. -Q., Wood C., Levy J. A., Cheng-Mayer C. 1990; The viral envelope gene is involved in macrophage tropism of a human immunodeficiency virus type-1 strain isolated from brain tissue. Journal of Virology 64:6148–6153
    [Google Scholar]
  20. Milich L., Margolin B., Swanstrom R. 1993; V3 loop of the HIV-1 env protein: interpreting sequencing variability. Journal of Virology 67:5623–5634
    [Google Scholar]
  21. 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 gpl20 outside the CD4-binding domain. Nature; London: 34869–73
    [Google Scholar]
  22. Page K. A., Stearns S. M., Littman D. R. 1992; Analysis of mutations in the V3 domain of gpl60 that affect fusion and infectivity. Journal of Virology 66:524–533
    [Google Scholar]
  23. Shioda T., Levy J. A., Cheng-Mayer C. 1991; Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions of the envelope gpl20 gene. Nature; London: 349167–169
    [Google Scholar]
  24. Stamatatos L., Cheng-Mayer C. 1993; Evidence that the structural conformation of envelope gpl20 affects HIV-1 infectivity, host range and syncytium forming ability. Journal of Virology 67:5635–5639
    [Google Scholar]
  25. Takeuchi Y., Akutsu M., Murayama K., Shimizu N., Hoshino H. 1991; Host range mutant of HIV-1: modification of cell tropism by a single point mutation at the neutralization epitope in the env gene. Journal of Virology 65:1710–1718
    [Google Scholar]
  26. Venkitaraman A. R. 1989; Use of modified T7 DNA polymerase for oligonucleotide site-directed mutagenesis. Nucleic Acids Research 17:3314
    [Google Scholar]
  27. York-Higgins D., Cheng-Mayer C., Bauer D., Levy J. A., Dina D. 1990; Human immunodeficiency virus type 1 cellular host range, replication and cytopathicity are linked to the envelope region of the viral genome. Journal of Virology 64:4016–4020
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-75-11-3249
Loading
/content/journal/jgv/10.1099/0022-1317-75-11-3249
Loading

Data & Media loading...

Most cited Most Cited RSS feed