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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Aug 15;89(16):7365–7369. doi: 10.1073/pnas.89.16.7365

Development of a quasispecies of human immunodeficiency virus type 1 in vivo.

K Cichutek 1, H Merget 1, S Norley 1, R Linde 1, W Kreuz 1, M Gahr 1, R Kurth 1
PMCID: PMC49710  PMID: 1502146

Abstract

During treatment with one specific batch of blood clotting factor IX, a number of hemophilia B patients in Germany recently became infected with human immunodeficiency virus type 1 (HIV-1). The nucleotide sequences of cloned HIV-1 envelope gene regions including the variable V3 loop and the V4 region derived from short-term virus cultures and directly from peripheral blood cells of these patients were shown to be highly homologous. Based on the assumption that the corresponding consensus sequence (termed HIV-1MBK) was identical to the genotype of the initially infecting virus, we were able to construct phylogenetic trees of the developing quasispecies in two patients studied in detail. True intermediates between input and multiply mutated genotypes were found in individual blood samples. Except for the initially infecting variant HIV-1MBK, variants found at 11 months postinfection had replaced those seen at 5 months postinfection. Variability early after infection was shown to cluster in two small regions located 3' of the V3 loop (i.e., outside the loop) and within the V4 region. This communication therefore describes the evolution of an HIV-1 quasispecies in humans starting from a single genotype.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baier M., Dittmar M. T., Cichutek K., Kurth R. Development of vivo of genetic variability of simian immunodeficiency virus. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8126–8130. doi: 10.1073/pnas.88.18.8126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Balfe P., Simmonds P., Ludlam C. A., Bishop J. O., Brown A. J. Concurrent evolution of human immunodeficiency virus type 1 in patients infected from the same source: rate of sequence change and low frequency of inactivating mutations. J Virol. 1990 Dec;64(12):6221–6233. doi: 10.1128/jvi.64.12.6221-6233.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burns D. P., Desrosiers R. C. Selection of genetic variants of simian immunodeficiency virus in persistently infected rhesus monkeys. J Virol. 1991 Apr;65(4):1843–1854. doi: 10.1128/jvi.65.4.1843-1854.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cichutek K., Norley S., Linde R., Kreuz W., Gahr M., Löwer J., von Wangenheim G., Kurth R. Lack of HIV-1 V3 region sequence diversity in two haemophiliac patients infected with a putative biologic clone of HIV-1. AIDS. 1991 Oct;5(10):1185–1187. doi: 10.1097/00002030-199110000-00005. [DOI] [PubMed] [Google Scholar]
  5. Goodenow M., Huet T., Saurin W., Kwok S., Sninsky J., Wain-Hobson S. HIV-1 isolates are rapidly evolving quasispecies: evidence for viral mixtures and preferred nucleotide substitutions. J Acquir Immune Defic Syndr. 1989;2(4):344–352. [PubMed] [Google Scholar]
  6. LaRosa G. J., Davide J. P., Weinhold K., Waterbury J. A., Profy A. T., Lewis J. A., Langlois A. J., Dreesman G. R., Boswell R. N., Shadduck P. Conserved sequence and structural elements in the HIV-1 principal neutralizing determinant. Science. 1990 Aug 24;249(4971):932–935. doi: 10.1126/science.2392685. [DOI] [PubMed] [Google Scholar]
  7. Li Y., Kappes J. C., Conway J. A., Price R. W., Shaw G. M., Hahn B. H. Molecular characterization of human immunodeficiency virus type 1 cloned directly from uncultured human brain tissue: identification of replication-competent and -defective viral genomes. J Virol. 1991 Aug;65(8):3973–3985. doi: 10.1128/jvi.65.8.3973-3985.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Martins L. P., Chenciner N., Asjö B., Meyerhans A., Wain-Hobson S. Independent fluctuation of human immunodeficiency virus type 1 rev and gp41 quasispecies in vivo. J Virol. 1991 Aug;65(8):4502–4507. doi: 10.1128/jvi.65.8.4502-4507.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. McNearney T., Westervelt P., Thielan B. J., Trowbridge D. B., 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. doi: 10.1073/pnas.87.5.1917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Meyerhans A., Cheynier R., Albert J., Seth M., Kwok S., Sninsky J., Morfeldt-Månson L., Asjö B., Wain-Hobson S. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell. 1989 Sep 8;58(5):901–910. doi: 10.1016/0092-8674(89)90942-2. [DOI] [PubMed] [Google Scholar]
  11. Modrow S., Hahn B. H., Shaw G. M., Gallo R. C., Wong-Staal F., Wolf H. Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions. J Virol. 1987 Feb;61(2):570–578. doi: 10.1128/jvi.61.2.570-578.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nara P. L., Smit L., Dunlop N., Hatch W., Merges M., Waters D., Kelliher J., Gallo R. C., Fischinger P. J., Goudsmit J. Emergence of viruses resistant to neutralization by V3-specific antibodies in experimental human immunodeficiency virus type 1 IIIB infection of chimpanzees. J Virol. 1990 Aug;64(8):3779–3791. doi: 10.1128/jvi.64.8.3779-3791.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Simmonds P., Balfe P., Ludlam C. A., Bishop J. O., Brown A. J. 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. doi: 10.1128/jvi.64.12.5840-5850.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Smith T. F., Srinivasan A., Schochetman G., Marcus M., Myers G. The phylogenetic history of immunodeficiency viruses. Nature. 1988 Jun 9;333(6173):573–575. doi: 10.1038/333573a0. [DOI] [PubMed] [Google Scholar]
  15. Starcich B. R., Hahn B. H., Shaw G. M., McNeely P. D., Modrow S., Wolf H., Parks E. S., Parks W. P., Josephs S. F., Gallo R. C. Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS. Cell. 1986 Jun 6;45(5):637–648. doi: 10.1016/0092-8674(86)90778-6. [DOI] [PubMed] [Google Scholar]

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