Abstract
The extent of nucleotide variation within the HIV-1 env hypervariable domains serves as a marker of virus genotypes within infected individuals and as a means to track transmission of the virus between individuals. We analyzed env V1 and V2 sequences in longitudinal samples from two HIV-1-infected mothers, each with three children infected by maternal transmission of the virus. Sequences in samples that were obtained from two infants at 2 d and 4 wk after birth displayed more variation in V1 and V2 than maternal samples obtained at the same times. Multiple HIV-1 genotypes were identified in each mother. In each family, multiple maternal HIV-1 genotypes were transmitted to the infants. Specific amino acid residues in the hypervariable domains were conserved within sequences from each family producing a family-specific amino acid signature pattern in V1 and V2. Viruses that were highly related to maternal viruses in signature pattern persisted for as long as 4 yr in the older children. Results support a model of transmission involving multiple HIV-1 genotypes with development of genetic variation from differential outgrowth and accumulation of genetic changes within each individual.
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- Andiman W. A., Simpson B. J., Olson B., Dember L., Silva T. J., Miller G. Rate of transmission of human immunodeficiency virus type 1 infection from mother to child and short-term outcome of neonatal infection. Results of a prospective cohort study. Am J Dis Child. 1990 Jul;144(7):758–766. doi: 10.1001/archpedi.1990.02150310026020. [DOI] [PubMed] [Google Scholar]
- Blanche S., Rouzioux C., Moscato M. L., Veber F., Mayaux M. J., Jacomet C., Tricoire J., Deville A., Vial M., Firtion G. A prospective study of infants born to women seropositive for human immunodeficiency virus type 1. HIV Infection in Newborns French Collaborative Study Group. N Engl J Med. 1989 Jun 22;320(25):1643–1648. doi: 10.1056/NEJM198906223202502. [DOI] [PubMed] [Google Scholar]
- Broliden P. A., Moschese V., Ljunggren K., Rosen J., Fundaro C., Plebani A., Jondal M., Rossi P., Wahren B. Diagnostic implication of specific immunoglobulin G patterns of children born to HIV-infected mothers. AIDS. 1989 Sep;3(9):577–582. doi: 10.1097/00002030-198909000-00004. [DOI] [PubMed] [Google Scholar]
- Burger H., Weiser B., Flaherty K., Gulla J., Nguyen P. N., Gibbs R. A. Evolution of human immunodeficiency virus type 1 nucleotide sequence diversity among close contacts. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11236–11240. doi: 10.1073/pnas.88.24.11236. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caldwell M. B., Rogers M. F. Epidemiology of pediatric HIV infection. Pediatr Clin North Am. 1991 Feb;38(1):1–16. doi: 10.1016/s0031-3955(16)38039-7. [DOI] [PubMed] [Google Scholar]
- Cichutek K., Merget H., Norley S., Linde R., Kreuz W., Gahr M., Kurth R. Development of a quasispecies of human immunodeficiency virus type 1 in vivo. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7365–7369. doi: 10.1073/pnas.89.16.7365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cowan M. J., Hellmann D., Chudwin D., Wara D. W., Chang R. S., Ammann A. J. Maternal transmission of acquired immune deficiency syndrome. Pediatrics. 1984 Mar;73(3):382–386. [PubMed] [Google Scholar]
- De Rossi A., Pasti M., Mammano F., Ometto L., Giaquinto C., Chieco-Bianchi L. Perinatal infection by human immunodeficiency virus type 1 (HIV-1): relationship between proviral copy number in vivo, viral properties in vitro, and clinical outcome. J Med Virol. 1991 Dec;35(4):283–289. doi: 10.1002/jmv.1890350414. [DOI] [PubMed] [Google Scholar]
- Delassus S., Cheynier R., Wain-Hobson S. Evolution of human immunodeficiency virus type 1 nef and long terminal repeat sequences over 4 years in vivo and in vitro. J Virol. 1991 Jan;65(1):225–231. doi: 10.1128/jvi.65.1.225-231.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Delassus S., Cheynier R., Wain-Hobson S. Nonhomogeneous distribution of human immunodeficiency virus type 1 proviruses in the spleen. J Virol. 1992 Sep;66(9):5642–5645. doi: 10.1128/jvi.66.9.5642-5645.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Devash Y., Calvelli T. A., Wood D. G., Reagan K. J., Rubinstein A. Vertical transmission of human immunodeficiency virus is correlated with the absence of high-affinity/avidity maternal antibodies to the gp120 principal neutralizing domain. Proc Natl Acad Sci U S A. 1990 May;87(9):3445–3449. doi: 10.1073/pnas.87.9.3445. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Embretson J., Zupancic M., Ribas J. L., Burke A., Racz P., Tenner-Racz K., Haase A. T. Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature. 1993 Mar 25;362(6418):359–362. doi: 10.1038/362359a0. [DOI] [PubMed] [Google Scholar]
- Fenyö E. M., Morfeldt-Månson L., Chiodi F., Lind B., von Gegerfelt A., Albert J., Olausson E., Asjö B. Distinct replicative and cytopathic characteristics of human immunodeficiency virus isolates. J Virol. 1988 Nov;62(11):4414–4419. doi: 10.1128/jvi.62.11.4414-4419.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fung M. S., Sun C. R., Gordon W. L., Liou R. S., Chang T. W., Sun W. N., Daar E. S., Ho D. D. Identification and characterization of a neutralization site within the second variable region of human immunodeficiency virus type 1 gp120. J Virol. 1992 Feb;66(2):848–856. doi: 10.1128/jvi.66.2.848-856.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goedert J. J., Duliège A. M., Amos C. I., Felton S., Biggar R. J. High risk of HIV-1 infection for first-born twins. The International Registry of HIV-exposed Twins. Lancet. 1991 Dec 14;338(8781):1471–1475. doi: 10.1016/0140-6736(91)92297-f. [DOI] [PubMed] [Google Scholar]
- Goedert J. J., Mendez H., Drummond J. E., Robert-Guroff M., Minkoff H. L., Holman S., Stevens R., Rubinstein A., Blattner W. A., Willoughby A. Mother-to-infant transmission of human immunodeficiency virus type 1: association with prematurity or low anti-gp120. Lancet. 1989 Dec 9;2(8676):1351–1354. doi: 10.1016/s0140-6736(89)91965-x. [DOI] [PubMed] [Google Scholar]
- 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]
- Goudsmit J., Back N. K., Nara P. L. Genomic diversity and antigenic variation of HIV-1: links between pathogenesis, epidemiology and vaccine development. FASEB J. 1991 Jul;5(10):2427–2436. doi: 10.1096/fasebj.5.10.2065891. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Kind C., Brändle B., Wyler C. A., Calame A., Rudin C., Schaad U. B., Schüpbach J., Senn H. P., Perrin L., Matter L. Epidemiology of vertically transmitted HIV-1 infection in Switzerland: results of a nationwide prospective study. Swiss Neonatal HIV Study Group. Eur J Pediatr. 1992 Jun;151(6):442–448. doi: 10.1007/BF01959360. [DOI] [PubMed] [Google Scholar]
- Kollmann T. R., Rubinstein A., Lyman W. D., Soeiro R., Goldstein H. Characterization of IgG and IgG subclass antibodies present in paired maternal and fetal serum which are directed against HIV-1 proteins. AIDS Res Hum Retroviruses. 1991 Oct;7(10):847–854. doi: 10.1089/aid.1991.7.847. [DOI] [PubMed] [Google Scholar]
- Kusumi K., Conway B., Cunningham S., Berson A., Evans C., Iversen A. K., Colvin D., Gallo M. V., Coutre S., Shpaer E. G. Human immunodeficiency virus type 1 envelope gene structure and diversity in vivo and after cocultivation in vitro. J Virol. 1992 Feb;66(2):875–885. doi: 10.1128/jvi.66.2.875-885.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Lamers S. L., Sleasman J. W., She J. X., Barrie K. A., Pomeroy S. M., Barrett D. J., Goodenow M. M. Independent variation and positive selection in env V1 and V2 domains within maternal-infant strains of human immunodeficiency virus type 1 in vivo. J Virol. 1993 Jul;67(7):3951–3960. doi: 10.1128/jvi.67.7.3951-3960.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leonard C. K., Spellman M. W., Riddle L., Harris R. J., Thomas J. N., Gregory T. J. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J Biol Chem. 1990 Jun 25;265(18):10373–10382. [PubMed] [Google Scholar]
- Ljunggren K., Moschese V., Broliden P. A., Giaquinto C., Quinti I., Fenyö E. M., Wahren B., Rossi P., Jondal M. Antibodies mediating cellular cytotoxicity and neutralization correlate with a better clinical stage in children born to human immunodeficiency virus-infected mothers. J Infect Dis. 1990 Feb;161(2):198–202. doi: 10.1093/infdis/161.2.198. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Michael N. L., Chang G., Ehrenberg P. K., Vahey M. T., Redfield R. R. HIV-1 proviral genotypes from the peripheral blood mononuclear cells of an infected patient are differentially represented in expressed sequences. J Acquir Immune Defic Syndr. 1993 Oct;6(10):1073–1085. [PubMed] [Google Scholar]
- 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]
- Nei M., Jin L. Variances of the average numbers of nucleotide substitutions within and between populations. Mol Biol Evol. 1989 May;6(3):290–300. doi: 10.1093/oxfordjournals.molbev.a040547. [DOI] [PubMed] [Google Scholar]
- Ou C. Y., Ciesielski C. A., Myers G., Bandea C. I., Luo C. C., Korber B. T., Mullins J. I., Schochetman G., Berkelman R. L., Economou A. N. Molecular epidemiology of HIV transmission in a dental practice. Science. 1992 May 22;256(5060):1165–1171. doi: 10.1126/science.256.5060.1165. [DOI] [PubMed] [Google Scholar]
- Pang S., Shlesinger Y., Daar E. S., Moudgil T., Ho D. D., Chen I. S. Rapid generation of sequence variation during primary HIV-1 infection. AIDS. 1992 May;6(5):453–460. doi: 10.1097/00002030-199205000-00003. [DOI] [PubMed] [Google Scholar]
- Pantaleo G., Graziosi C., Demarest J. F., Butini L., Montroni M., Fox C. H., Orenstein J. M., Kotler D. P., Fauci A. S. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature. 1993 Mar 25;362(6418):355–358. doi: 10.1038/362355a0. [DOI] [PubMed] [Google Scholar]
- Parekh B. S., Shaffer N., Pau C. P., Abrams E., Thomas P., Pollack H., Bamji M., Kaul A., Schochetman G., Rogers M. Lack of correlation between maternal antibodies to V3 loop peptides of gp120 and perinatal HIV-1 transmission. The NYC Perinatal HIV Transmission Collaborative Study. AIDS. 1991 Oct;5(10):1179–1184. doi: 10.1097/00002030-199110000-00004. [DOI] [PubMed] [Google Scholar]
- Pedroza Martins L., Chenciner N., Wain-Hobson S. Complex intrapatient sequence variation in the V1 and V2 hypervariable regions of the HIV-1 gp 120 envelope sequence. Virology. 1992 Dec;191(2):837–845. doi: 10.1016/0042-6822(92)90259-r. [DOI] [PubMed] [Google Scholar]
- Piatak M., Jr, Saag M. S., Yang L. C., Clark S. J., Kappes J. C., Luk K. C., Hahn B. H., Shaw G. M., Lifson J. D. High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. Science. 1993 Mar 19;259(5102):1749–1754. doi: 10.1126/science.8096089. [DOI] [PubMed] [Google Scholar]
- Pollack M. S., Kirkpatrick D., Kapoor N., Dupont B., O'Reilly R. J. Identification by HLA typing of intrauterine-derived maternal T cells in four patients with severe combined immunodeficiency. N Engl J Med. 1982 Sep 9;307(11):662–666. doi: 10.1056/NEJM198209093071106. [DOI] [PubMed] [Google Scholar]
- Rossi P., Moschese V., Broliden P. A., Fundaró C., Quinti I., Plebani A., Giaquinto C., Tovo P. A., Ljunggren K., Rosen J. Presence of maternal antibodies to human immunodeficiency virus 1 envelope glycoprotein gp120 epitopes correlates with the uninfected status of children born to seropositive mothers. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8055–8058. doi: 10.1073/pnas.86.20.8055. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rossi P., Moschese V., de Rossi A., Wahren B., Jansson M., Lombardi V., Wigzell H. Maternal antibody epitope mapping in mother-to-child transmission of HIV. Adv Exp Med Biol. 1991;303:47–52. doi: 10.1007/978-1-4684-6000-1_6. [DOI] [PubMed] [Google Scholar]
- Ryder R. W., Nsa W., Hassig S. E., Behets F., Rayfield M., Ekungola B., Nelson A. M., Mulenda U., Francis H., Mwandagalirwa K. Perinatal transmission of the human immunodeficiency virus type 1 to infants of seropositive women in Zaire. N Engl J Med. 1989 Jun 22;320(25):1637–1642. doi: 10.1056/NEJM198906223202501. [DOI] [PubMed] [Google Scholar]
- Saag M. S., Crain M. J., Decker W. D., Campbell-Hill S., Robinson S., Brown W. E., Leuther M., Whitley R. J., Hahn B. H., Shaw G. M. High-level viremia in adults and children infected with human immunodeficiency virus: relation to disease stage and CD4+ lymphocyte levels. J Infect Dis. 1991 Jul;164(1):72–80. doi: 10.1093/infdis/164.1.72. [DOI] [PubMed] [Google Scholar]
- Scarlatti G., Leitner T., Halapi E., Wahlberg J., Marchisio P., Clerici-Schoeller M. A., Wigzell H., Fenyö E. M., Albert J., Uhlén M. Comparison of variable region 3 sequences of human immunodeficiency virus type 1 from infected children with the RNA and DNA sequences of the virus populations of their mothers. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1721–1725. doi: 10.1073/pnas.90.5.1721. [DOI] [PMC free article] [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]
- Scott G. B., Fischl M. A., Klimas N., Fletcher M. A., Dickinson G. M., Levine R. S., Parks W. P. Mothers of infants with the acquired immunodeficiency syndrome. Evidence for both symptomatic and asymptomatic carriers. JAMA. 1985 Jan 18;253(3):363–366. [PubMed] [Google Scholar]
- Scott G. B., Hutto C., Makuch R. W., Mastrucci M. T., O'Connor T., Mitchell C. D., Trapido E. J., Parks W. P. Survival in children with perinatally acquired human immunodeficiency virus type 1 infection. N Engl J Med. 1989 Dec 28;321(26):1791–1796. doi: 10.1056/NEJM198912283212604. [DOI] [PubMed] [Google Scholar]
- Sharpless N. E., O'Brien W. A., Verdin E., Kufta C. V., Chen I. S., Dubois-Dalcq M. Human immunodeficiency virus type 1 tropism for brain microglial cells is determined by a region of the env glycoprotein that also controls macrophage tropism. J Virol. 1992 Apr;66(4):2588–2593. doi: 10.1128/jvi.66.4.2588-2593.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- She J. X., Boehme S. A., Wang T. W., Bonhomme F., Wakeland E. K. Amplification of major histocompatibility complex class II gene diversity by intraexonic recombination. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):453–457. doi: 10.1073/pnas.88.2.453. [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]
- 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]
- 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]
- Sullivan N., Thali M., Furman C., Ho D. D., Sodroski J. 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. J Virol. 1993 Jun;67(6):3674–3679. doi: 10.1128/jvi.67.6.3674-3679.1993. [DOI] [PMC free article] [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]
- 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]
- 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]
- van Tijn D. A., Boucher C. A., Bakker M., Goudsmit J. Antigenicity of linear B-cell epitopes in the C1, V1, and V3 region of HIV-1 gp 120. J Acquir Immune Defic Syndr. 1989;2(3):303–306. [PubMed] [Google Scholar]
