Abstract
Phylogenetic analysis was used to study in vivo genetic variation of the V3 region of human immunodeficiency virus type 1 in relation to disease progression in six infants with vertically acquired human immunodeficiency virus type 1 infection. Nucleotide sequences from each infant formed a monophyletic group with similar average branch lengths separating the sets of sequences. In contrast to the star-shaped phylogeny characteristic of interinfant viral evolution, the shape of the phylogeny formed by sequences from the infants who developed AIDS tended to be linear. A computer program, DISTRATE, was written to analyze changes in DNA distance values over time. For the six infants, the rate of divergence from the initial variant was inversely correlated with CD4 cell counts averaged over the first 11 to 15 months of life (r = -0.87, P = 0.024). To uncover evolutionary relationships that might be dictated by protein structure and function, tree-building methods were applied to inferred amino acid sequences. Trees constructed from the full-length protein fragment (92 amino acids) showed that viruses from each infant formed a monophyletic group. Unexpectedly, V3 loop protein sequences (35 amino acids) that were found at later time points from the two infants who developed AIDS clustered together. Furthermore, these sequences uniquely shared amino acids that have been shown to confer a T-cell line tropic phenotype. The evolutionary pattern suggests that viruses from these infants with AIDS acquired similar and possibly more virulent phenotypes.
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- Ahmad N., Baroudy B. M., Baker R. C., Chappey C. Genetic analysis of human immunodeficiency virus type 1 envelope V3 region isolates from mothers and infants after perinatal transmission. J Virol. 1995 Feb;69(2):1001–1012. doi: 10.1128/jvi.69.2.1001-1012.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Albert J., Wahlberg J., Leitner T., Escanilla D., Uhlén M. Analysis of a rape case by direct sequencing of the human immunodeficiency virus type 1 pol and gag genes. J Virol. 1994 Sep;68(9):5918–5924. doi: 10.1128/jvi.68.9.5918-5924.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alizon M., Wain-Hobson S., Montagnier L., Sonigo P. Genetic variability of the AIDS virus: nucleotide sequence analysis of two isolates from African patients. Cell. 1986 Jul 4;46(1):63–74. doi: 10.1016/0092-8674(86)90860-3. [DOI] [PubMed] [Google Scholar]
- Ambrose M. R., Hetherington S. V., Watson A. S., Scroggs R. A., Portner A. Molecular evolution of the F glycoprotein of human parainfluenza virus type 1. J Infect Dis. 1995 Apr;171(4):851–856. doi: 10.1093/infdis/171.4.851. [DOI] [PubMed] [Google Scholar]
- Bassam B. J., Caetano-Anollés G., Gresshoff P. M. Fast and sensitive silver staining of DNA in polyacrylamide gels. Anal Biochem. 1991 Jul;196(1):80–83. doi: 10.1016/0003-2697(91)90120-i. [DOI] [PubMed] [Google Scholar]
- Briant L., Wade C. M., Puel J., Brown A. J., Guyader M. Analysis of envelope sequence variants suggests multiple mechanisms of mother-to-child transmission of human immunodeficiency virus type 1. J Virol. 1995 Jun;69(6):3778–3788. doi: 10.1128/jvi.69.6.3778-3788.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buonagurio D. A., Nakada S., Parvin J. D., Krystal M., Palese P., Fitch W. M. Evolution of human influenza A viruses over 50 years: rapid, uniform rate of change in NS gene. Science. 1986 May 23;232(4753):980–982. doi: 10.1126/science.2939560. [DOI] [PubMed] [Google Scholar]
- Cabot E. L., Beckenbach A. T. Simultaneous editing of multiple nucleic acid and protein sequences with ESEE. Comput Appl Biosci. 1989 Jul;5(3):233–234. doi: 10.1093/bioinformatics/5.3.233. [DOI] [PubMed] [Google Scholar]
- Cheng-Mayer C., Seto D., Tateno M., Levy J. A. Biologic features of HIV-1 that correlate with virulence in the host. Science. 1988 Apr 1;240(4848):80–82. doi: 10.1126/science.2832945. [DOI] [PubMed] [Google Scholar]
- 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. doi: 10.1128/jvi.66.11.6547-6554.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cornelissen M., Mulder-Kampinga G., Veenstra J., Zorgdrager F., Kuiken C., Hartman S., Dekker J., van der Hoek L., Sol C., Coutinho R. Syncytium-inducing (SI) phenotype suppression at seroconversion after intramuscular inoculation of a non-syncytium-inducing/SI phenotypically mixed human immunodeficiency virus population. J Virol. 1995 Mar;69(3):1810–1818. doi: 10.1128/jvi.69.3.1810-1818.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Delwart E. L., Shpaer E. G., Louwagie J., McCutchan F. E., Grez M., Rübsamen-Waigmann H., Mullins J. I. Genetic relationships determined by a DNA heteroduplex mobility assay: analysis of HIV-1 env genes. Science. 1993 Nov 19;262(5137):1257–1261. doi: 10.1126/science.8235655. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Hahn B. H., Shaw G. M., Taylor M. E., Redfield R. R., Markham P. D., Salahuddin S. Z., Wong-Staal F., Gallo R. C., Parks E. S., Parks W. P. Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS. Science. 1986 Jun 20;232(4757):1548–1553. doi: 10.1126/science.3012778. [DOI] [PubMed] [Google Scholar]
- Holmes E. C., Zhang L. Q., Simmonds P., Ludlam C. A., Brown A. J. Convergent and divergent sequence evolution in the surface envelope glycoprotein of human immunodeficiency virus type 1 within a single infected patient. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4835–4839. doi: 10.1073/pnas.89.11.4835. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holmes E. C., Zhang L. Q., Simmonds P., Rogers A. S., Brown A. J. Molecular investigation of human immunodeficiency virus (HIV) infection in a patient of an HIV-infected surgeon. J Infect Dis. 1993 Jun;167(6):1411–1414. doi: 10.1093/infdis/167.6.1411. [DOI] [PubMed] [Google Scholar]
- Hwang S. S., Boyle T. J., Lyerly H. K., Cullen B. R. Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1. Science. 1991 Jul 5;253(5015):71–74. doi: 10.1126/science.1905842. [DOI] [PubMed] [Google Scholar]
- Korber B. T., Farber R. M., Wolpert D. H., Lapedes A. S. Covariation of mutations in the V3 loop of human immunodeficiency virus type 1 envelope protein: an information theoretic analysis. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7176–7180. doi: 10.1073/pnas.90.15.7176. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Korber B. T., MacInnes K., Smith R. F., Myers G. Mutational trends in V3 loop protein sequences observed in different genetic lineages of human immunodeficiency virus type 1. J Virol. 1994 Oct;68(10):6730–6744. doi: 10.1128/jvi.68.10.6730-6744.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuiken C. L., de Jong J. J., Baan E., Keulen W., Tersmette M., Goudsmit J. Evolution of the V3 envelope domain in proviral sequences and isolates of human immunodeficiency virus type 1 during transition of the viral biological phenotype. J Virol. 1992 Jul;66(7):4622–4627. doi: 10.1128/jvi.66.7.4622-4627.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Louwagie J., McCutchan F. E., Peeters M., Brennan T. P., Sanders-Buell E., Eddy G. A., van der Groen G., Fransen K., Gershy-Damet G. M., Deleys R. Phylogenetic analysis of gag genes from 70 international HIV-1 isolates provides evidence for multiple genotypes. AIDS. 1993 Jun;7(6):769–780. doi: 10.1097/00002030-199306000-00003. [DOI] [PubMed] [Google Scholar]
- Mammano F., Salvatori F., Ometto L., Panozzo M., Chieco-Bianchi L., De Rossi A. Relationship between the V3 loop and the phenotypes of human immunodeficiency virus type 1 (HIV-1) isolates from children perinatally infected with HIV-1. J Virol. 1995 Jan;69(1):82–92. doi: 10.1128/jvi.69.1.82-92.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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. doi: 10.1073/pnas.89.21.10247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Milich L., Margolin B., Swanstrom R. V3 loop of the human immunodeficiency virus type 1 Env protein: interpreting sequence variability. J Virol. 1993 Sep;67(9):5623–5634. doi: 10.1128/jvi.67.9.5623-5634.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Myers G., MacInnes K., Korber B. The emergence of simian/human immunodeficiency viruses. AIDS Res Hum Retroviruses. 1992 Mar;8(3):373–386. doi: 10.1089/aid.1992.8.373. [DOI] [PubMed] [Google Scholar]
- Nei M., Gojobori T. Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol. 1986 Sep;3(5):418–426. doi: 10.1093/oxfordjournals.molbev.a040410. [DOI] [PubMed] [Google Scholar]
- Nowak M. A., Anderson R. M., McLean A. R., Wolfs T. F., Goudsmit J., May R. M. Antigenic diversity thresholds and the development of AIDS. Science. 1991 Nov 15;254(5034):963–969. doi: 10.1126/science.1683006. [DOI] [PubMed] [Google Scholar]
- Oka S., Ida S., Shioda T., Takebe Y., Kobayashi N., Shibuya Y., Ohyama K., Momota K., Kimura S., Shimada K. Genetic analysis of HIV-1 during rapid progression to AIDS in an apparently healthy man. AIDS Res Hum Retroviruses. 1994 Mar;10(3):271–277. doi: 10.1089/aid.1994.10.271. [DOI] [PubMed] [Google Scholar]
- Rübsamen-Waigmann H., von Briesen H., Holmes H., Björndal A., Korber B., Esser R., Ranjbar S., Tomlinson P., Galvao-Castro B., Karita E. Standard conditions of virus isolation reveal biological variability of HIV type 1 in different regions of the world. WHO Network for HIV Isolation and Characterization. AIDS Res Hum Retroviruses. 1994 Nov;10(11):1401–1408. doi: 10.1089/aid.1994.10.1401. [DOI] [PubMed] [Google Scholar]
- 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]
- Shioda T., Levy J. A., 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. doi: 10.1038/349167a0. [DOI] [PubMed] [Google Scholar]
- Shioda T., Levy J. A., Cheng-Mayer C. Small amino acid changes in the V3 hypervariable region of gp120 can affect the T-cell-line and macrophage tropism of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9434–9438. doi: 10.1073/pnas.89.20.9434. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shpaer E. G., Mullins J. I. Rates of amino acid change in the envelope protein correlate with pathogenicity of primate lentiviruses. J Mol Evol. 1993 Jul;37(1):57–65. doi: 10.1007/BF00170462. [DOI] [PubMed] [Google Scholar]
- Simmonds P., Zhang L. Q., McOmish F., Balfe P., Ludlam C. A., Brown A. J. 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. doi: 10.1128/jvi.65.11.6266-6276.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stewart C. B., Schilling J. W., Wilson A. C. Adaptive evolution in the stomach lysozymes of foregut fermenters. 1987 Nov 26-Dec 2Nature. 330(6146):401–404. doi: 10.1038/330401a0. [DOI] [PubMed] [Google Scholar]
- Tersmette M., Gruters R. A., de Wolf F., de Goede R. E., Lange J. M., Schellekens P. T., Goudsmit J., Huisman H. G., Miedema F. Evidence for a role of virulent human immunodeficiency virus (HIV) variants in the pathogenesis of acquired immunodeficiency syndrome: studies on sequential HIV isolates. J Virol. 1989 May;63(5):2118–2125. doi: 10.1128/jvi.63.5.2118-2125.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wain-Hobson S. Human immunodeficiency virus type 1 quasispecies in vivo and ex vivo. Curr Top Microbiol Immunol. 1992;176:181–193. doi: 10.1007/978-3-642-77011-1_12. [DOI] [PubMed] [Google Scholar]
- Westervelt P., Trowbridge D. B., Epstein L. G., Blumberg B. M., Li Y., Hahn B. H., Shaw G. M., Price R. W., Ratner L. Macrophage tropism determinants of human immunodeficiency virus type 1 in vivo. J Virol. 1992 Apr;66(4):2577–2582. doi: 10.1128/jvi.66.4.2577-2582.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willey R. L., Theodore T. S., Martin M. A. Amino acid substitutions in the human immunodeficiency virus type 1 gp120 V3 loop that change viral tropism also alter physical and functional properties of the virion envelope. J Virol. 1994 Jul;68(7):4409–4419. doi: 10.1128/jvi.68.7.4409-4419.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolfs T. F., de Jong J. J., Van den Berg H., Tijnagel J. M., Krone W. J., Goudsmit J. Evolution of sequences encoding the principal neutralization epitope of human immunodeficiency virus 1 is host dependent, rapid, and continuous. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9938–9942. doi: 10.1073/pnas.87.24.9938. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolinsky S. M., Wike C. M., Korber B. T., Hutto C., Parks W. P., Rosenblum L. L., Kunstman K. J., Furtado M. R., Muñoz J. L. Selective transmission of human immunodeficiency virus type-1 variants from mothers to infants. Science. 1992 Feb 28;255(5048):1134–1137. doi: 10.1126/science.1546316. [DOI] [PubMed] [Google Scholar]
- Zhang L. Q., MacKenzie P., Cleland A., Holmes E. C., Brown A. J., 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. doi: 10.1128/jvi.67.6.3345-3356.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- de Jong J. J., 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. doi: 10.1128/jvi.66.2.757-765.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]