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. 1992 Nov;66(11):6587–6600. doi: 10.1128/jvi.66.11.6587-6600.1992

Complete nucleotide sequence, genome organization, and biological properties of human immunodeficiency virus type 1 in vivo: evidence for limited defectiveness and complementation.

Y Li 1, H Hui 1, C J Burgess 1, R W Price 1, P M Sharp 1, B H Hahn 1, G M Shaw 1
PMCID: PMC240154  PMID: 1404605

Abstract

Previous studies of the genetic and biologic characteristics of human immunodeficiency virus type 1 (HIV-1) have by necessity used tissue culture-derived virus. We recently reported the molecular cloning of four full-length HIV-1 genomes directly from uncultured human brain tissue (Y. Li, J. C. Kappes, J. A. Conway, R. W. Price, G. M. Shaw, and B. H. Hahn, J. Virol. 65:3973-3985, 1991). In this report, we describe the biologic properties of these four clones and the complete nucleotide sequences and genome organization of two of them. Clones HIV-1YU-2 and HIV-1YU-10 were 9,174 and 9,176 nucleotides in length, differed by 0.26% in nucleotide sequence, and except for a frameshift mutation in the pol gene in HIV-1YU-10, contained open reading frames corresponding to 5'-gag-pol-vif-vpr-tat-rev-vpu-env-nef-3' flanked by long terminal repeats. HIV-1YU-2 was fully replication competent, while HIV-1YU-10 and two other clones, HIV-1YU-21 and HIV-1YU-32, were defective. All three defective clones, however, when transfected into Cos-1 cells in any pairwise combination, yielded virions that were replication competent and transmissible by cell-free passage. The cellular host range of HIV-1YU-2 was strictly limited to primary T lymphocytes and monocyte-macrophages, a property conferred by its external envelope glycoprotein. Phylogenetic analyses of HIV-1YU-2 gene sequences revealed this virus to be a member of the North American/European HIV-1 subgroup, with specific similarity to other monocyte-tropic viruses in its V3 envelope amino acid sequence. These results indicate that HIV-1 infection of brain is characterized by the persistence of mixtures of fully competent, minimally defective, and more substantially altered viral forms and that complementation among them is readily attainable. In addition, the limited degree of genotypic heterogeneity observed among HIV-1YU and other brain-derived viruses and their preferential tropism for monocyte-macrophages suggest that viral replication within the central nervous system may differ from that within the peripheral lymphoid compartment in significant and clinically important ways. The availability of genetically and biologically well characterized HIV-1 clones from uncultured human tissue should facilitate future studies of virus-cell interactions relevant to viral pathogenesis and drug and vaccine development.

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Selected References

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  1. Albert J., Abrahamsson B., Nagy K., Aurelius E., Gaines H., Nyström G., Fenyö E. M. Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera. AIDS. 1990 Feb;4(2):107–112. doi: 10.1097/00002030-199002000-00002. [DOI] [PubMed] [Google Scholar]
  2. Allan J. S., Coligan J. E., Lee T. H., McLane M. F., Kanki P. J., Groopman J. E., Essex M. A new HTLV-III/LAV encoded antigen detected by antibodies from AIDS patients. Science. 1985 Nov 15;230(4727):810–813. doi: 10.1126/science.2997921. [DOI] [PubMed] [Google Scholar]
  3. Ameisen J. C., Capron A. Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis. Immunol Today. 1991 Apr;12(4):102–105. doi: 10.1016/0167-5699(91)90092-8. [DOI] [PubMed] [Google Scholar]
  4. Aziz D. C., Hanna Z., Jolicoeur P. Severe immunodeficiency disease induced by a defective murine leukaemia virus. Nature. 1989 Apr 6;338(6215):505–508. doi: 10.1038/338505a0. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Bathurst I. C., Chester N., Gibson H. L., Dennis A. F., Steimer K. S., Barr P. J. N myristylation of the human immunodeficiency virus type 1 gag polyprotein precursor in Saccharomyces cerevisiae. J Virol. 1989 Jul;63(7):3176–3179. doi: 10.1128/jvi.63.7.3176-3179.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bess J. W., Jr, Powell P. J., Issaq H. J., Schumack L. J., Grimes M. K., Henderson L. E., Arthur L. O. Tightly bound zinc in human immunodeficiency virus type 1, human T-cell leukemia virus type I, and other retroviruses. J Virol. 1992 Feb;66(2):840–847. doi: 10.1128/jvi.66.2.840-847.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bethea J. R., Chung I. Y., Sparacio S. M., Gillespie G. Y., Benveniste E. N. Interleukin-1 beta induction of tumor necrosis factor-alpha gene expression in human astroglioma cells. J Neuroimmunol. 1992 Feb;36(2-3):179–191. doi: 10.1016/0165-5728(92)90049-q. [DOI] [PubMed] [Google Scholar]
  9. Bethea J. R., Gillespie G. Y., Chung I. Y., Benveniste E. N. Tumor necrosis factor production and receptor expression by a human malignant glioma cell line, D54-MG. J Neuroimmunol. 1990 Nov;30(1):1–13. doi: 10.1016/0165-5728(90)90047-q. [DOI] [PubMed] [Google Scholar]
  10. Boucher C. A., O'Sullivan E., Mulder J. W., Ramautarsing C., Kellam P., Darby G., Lange J. M., Goudsmit J., Larder B. A. Ordered appearance of zidovudine resistance mutations during treatment of 18 human immunodeficiency virus-positive subjects. J Infect Dis. 1992 Jan;165(1):105–110. doi: 10.1093/infdis/165.1.105. [DOI] [PubMed] [Google Scholar]
  11. Charneau P., Clavel F. A single-stranded gap in human immunodeficiency virus unintegrated linear DNA defined by a central copy of the polypurine tract. J Virol. 1991 May;65(5):2415–2421. doi: 10.1128/jvi.65.5.2415-2421.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chattopadhyay S. K., Morse H. C., 3rd, Makino M., Ruscetti S. K., Hartley J. W. Defective virus is associated with induction of murine retrovirus-induced immunodeficiency syndrome. Proc Natl Acad Sci U S A. 1989 May;86(10):3862–3866. doi: 10.1073/pnas.86.10.3862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Clark S. J., Saag M. S., Decker W. D., Campbell-Hill S., Roberson J. L., Veldkamp P. J., Kappes J. C., Hahn B. H., Shaw G. M. High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. N Engl J Med. 1991 Apr 4;324(14):954–960. doi: 10.1056/NEJM199104043241404. [DOI] [PubMed] [Google Scholar]
  15. Coombs R. W., Collier A. C., Allain J. P., Nikora B., Leuther M., Gjerset G. F., Corey L. Plasma viremia in human immunodeficiency virus infection. N Engl J Med. 1989 Dec 14;321(24):1626–1631. doi: 10.1056/NEJM198912143212402. [DOI] [PubMed] [Google Scholar]
  16. Daar E. S., Li X. L., Moudgil T., Ho D. D. High concentrations of recombinant soluble CD4 are required to neutralize primary human immunodeficiency virus type 1 isolates. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6574–6578. doi: 10.1073/pnas.87.17.6574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Daar E. S., Moudgil T., Meyer R. D., Ho D. D. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. N Engl J Med. 1991 Apr 4;324(14):961–964. doi: 10.1056/NEJM199104043241405. [DOI] [PubMed] [Google Scholar]
  18. DeCarli C., Fugate L., Falloon J., Eddy J., Katz D. A., Friedland R. P., Rapoport S. I., Brouwers P., Pizzo P. A. Brain growth and cognitive improvement in children with human immunodeficiency virus-induced encephalopathy after 6 months of continuous infusion zidovudine therapy. J Acquir Immune Defic Syndr. 1991;4(6):585–592. [PubMed] [Google Scholar]
  19. Desrosiers R. C. HIV with multiple gene deletions as a live attenuated vaccine for AIDS. AIDS Res Hum Retroviruses. 1992 Mar;8(3):411–421. doi: 10.1089/aid.1992.8.411. [DOI] [PubMed] [Google Scholar]
  20. Di Persio J. F., Brennan J. K., Lichtman M. A., Speiser B. L. Human cell lines that elaborate colon-stimulating activity for the marrow cells of man and other species. Blood. 1978 Mar;51(3):507–519. [PubMed] [Google Scholar]
  21. Epstein L. G., Kuiken C., Blumberg B. M., Hartman S., Sharer L. R., Clement M., Goudsmit J. HIV-1 V3 domain variation in brain and spleen of children with AIDS: tissue-specific evolution within host-determined quasispecies. Virology. 1991 Feb;180(2):583–590. doi: 10.1016/0042-6822(91)90072-j. [DOI] [PubMed] [Google Scholar]
  22. Fauci A. S., Schnittman S. M., Poli G., Koenig S., Pantaleo G. NIH conference. Immunopathogenic mechanisms in human immunodeficiency virus (HIV) infection. Ann Intern Med. 1991 Apr 15;114(8):678–693. doi: 10.7326/0003-4819-114-8-678. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Fischl M. A., Richman D. D., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Schooley R. T. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):185–191. doi: 10.1056/NEJM198707233170401. [DOI] [PubMed] [Google Scholar]
  25. Fischl M. A., Richman D. D., Hansen N., Collier A. C., Carey J. T., Para M. F., Hardy W. D., Dolin R., Powderly W. G., Allan J. D. The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection. A double-blind, placebo-controlled trial. The AIDS Clinical Trials Group. Ann Intern Med. 1990 May 15;112(10):727–737. doi: 10.7326/0003-4819-112-10-727. [DOI] [PubMed] [Google Scholar]
  26. Fisher A. G., Collalti E., Ratner L., Gallo R. C., Wong-Staal F. A molecular clone of HTLV-III with biological activity. Nature. 1985 Jul 18;316(6025):262–265. doi: 10.1038/316262a0. [DOI] [PubMed] [Google Scholar]
  27. Franza B. R., Jr, Rauscher F. J., 3rd, Josephs S. F., Curran T. The Fos complex and Fos-related antigens recognize sequence elements that contain AP-1 binding sites. Science. 1988 Mar 4;239(4844):1150–1153. doi: 10.1126/science.2964084. [DOI] [PubMed] [Google Scholar]
  28. Gabuzda D. H., Ho D. D., de la Monte S. M., Hirsch M. S., Rota T. R., Sobel R. A. Immunohistochemical identification of HTLV-III antigen in brains of patients with AIDS. Ann Neurol. 1986 Sep;20(3):289–295. doi: 10.1002/ana.410200304. [DOI] [PubMed] [Google Scholar]
  29. Gao F., Yue L., White A. T., Pappas P. G., Barchue J., Hanson A. P., Greene B. M., Sharp P. M., Shaw G. M., Hahn B. H. Human infection by genetically diverse SIVSM-related HIV-2 in west Africa. Nature. 1992 Aug 6;358(6386):495–499. doi: 10.1038/358495a0. [DOI] [PubMed] [Google Scholar]
  30. Gartner S., Markovits P., Markovitz D. M., Betts R. F., Popovic M. Virus isolation from and identification of HTLV-III/LAV-producing cells in brain tissue from a patient with AIDS. JAMA. 1986 Nov 7;256(17):2365–2371. [PubMed] [Google Scholar]
  31. Gartner S., Markovits P., Markovitz D. M., Kaplan M. H., Gallo R. C., Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science. 1986 Jul 11;233(4760):215–219. doi: 10.1126/science.3014648. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Greene W. C. The molecular biology of human immunodeficiency virus type 1 infection. N Engl J Med. 1991 Jan 31;324(5):308–317. doi: 10.1056/NEJM199101313240506. [DOI] [PubMed] [Google Scholar]
  34. Guy B., Kieny M. P., Riviere Y., Le Peuch C., Dott K., Girard M., Montagnier L., Lecocq J. P. HIV F/3' orf encodes a phosphorylated GTP-binding protein resembling an oncogene product. Nature. 1987 Nov 19;330(6145):266–269. doi: 10.1038/330266a0. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Harouse J. M., Bhat S., Spitalnik S. L., Laughlin M., Stefano K., Silberberg D. H., Gonzalez-Scarano F. Inhibition of entry of HIV-1 in neural cell lines by antibodies against galactosyl ceramide. Science. 1991 Jul 19;253(5017):320–323. doi: 10.1126/science.1857969. [DOI] [PubMed] [Google Scholar]
  37. Higgins D. G., Bleasby A. J., Fuchs R. CLUSTAL V: improved software for multiple sequence alignment. Comput Appl Biosci. 1992 Apr;8(2):189–191. doi: 10.1093/bioinformatics/8.2.189. [DOI] [PubMed] [Google Scholar]
  38. Higgins D. G., Sharp P. M. CLUSTAL: a package for performing multiple sequence alignment on a microcomputer. Gene. 1988 Dec 15;73(1):237–244. doi: 10.1016/0378-1119(88)90330-7. [DOI] [PubMed] [Google Scholar]
  39. Ho D. D., Bredesen D. E., Vinters H. V., Daar E. S. The acquired immunodeficiency syndrome (AIDS) dementia complex. Ann Intern Med. 1989 Sep 1;111(5):400–410. doi: 10.7326/0003-4819-111-5-400. [DOI] [PubMed] [Google Scholar]
  40. Ho D. D., Moudgil T., Alam M. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N Engl J Med. 1989 Dec 14;321(24):1621–1625. doi: 10.1056/NEJM198912143212401. [DOI] [PubMed] [Google Scholar]
  41. Ho D. D., Pomerantz R. J., Kaplan J. C. Pathogenesis of infection with human immunodeficiency virus. N Engl J Med. 1987 Jul 30;317(5):278–286. doi: 10.1056/NEJM198707303170505. [DOI] [PubMed] [Google Scholar]
  42. Hu W. S., Temin H. M. Genetic consequences of packaging two RNA genomes in one retroviral particle: pseudodiploidy and high rate of genetic recombination. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1556–1560. doi: 10.1073/pnas.87.4.1556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. 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]
  44. Inoue M., Hoxie J. A., Reddy M. V., Srinivasan A., Reddy E. P. Mechanisms associated with the generation of biologically active human immunodeficiency virus type 1 particles from defective proviruses. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2278–2282. doi: 10.1073/pnas.88.6.2278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Jones K. A., Kadonaga J. T., Luciw P. A., Tjian R. Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1. Science. 1986 May 9;232(4751):755–759. doi: 10.1126/science.3008338. [DOI] [PubMed] [Google Scholar]
  46. Jones K. A., Luciw P. A., Duchange N. Structural arrangements of transcription control domains within the 5'-untranslated leader regions of the HIV-1 and HIV-2 promoters. Genes Dev. 1988 Sep;2(9):1101–1114. doi: 10.1101/gad.2.9.1101. [DOI] [PubMed] [Google Scholar]
  47. Kellam P., Boucher C. A., Larder B. A. Fifth mutation in human immunodeficiency virus type 1 reverse transcriptase contributes to the development of high-level resistance to zidovudine. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1934–1938. doi: 10.1073/pnas.89.5.1934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Kestler H. W., 3rd, Ringler D. J., Mori K., Panicali D. L., Sehgal P. K., Daniel M. D., Desrosiers R. C. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell. 1991 May 17;65(4):651–662. doi: 10.1016/0092-8674(91)90097-i. [DOI] [PubMed] [Google Scholar]
  49. Koller C. A., King G. W., Hurtubise P. E., Sagone A. L., LoBuglio A. F. Characterization of glass adherent human mononuclear cells. J Immunol. 1973 Nov;111(5):1610–1612. [PubMed] [Google Scholar]
  50. Koyanagi Y., Miles S., Mitsuyasu R. T., Merrill J. E., Vinters H. V., Chen I. S. Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science. 1987 May 15;236(4803):819–822. doi: 10.1126/science.3646751. [DOI] [PubMed] [Google Scholar]
  51. 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]
  52. 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]
  53. Larder B. A., Darby G., Richman D. D. HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science. 1989 Mar 31;243(4899):1731–1734. doi: 10.1126/science.2467383. [DOI] [PubMed] [Google Scholar]
  54. Larder B. A., Kemp S. D. Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT). Science. 1989 Dec 1;246(4934):1155–1158. doi: 10.1126/science.2479983. [DOI] [PubMed] [Google Scholar]
  55. Lever A., Gottlinger H., Haseltine W., Sodroski J. Identification of a sequence required for efficient packaging of human immunodeficiency virus type 1 RNA into virions. J Virol. 1989 Sep;63(9):4085–4087. doi: 10.1128/jvi.63.9.4085-4087.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Li W. H., Tanimura M., Sharp P. M. Rates and dates of divergence between AIDS virus nucleotide sequences. Mol Biol Evol. 1988 Jul;5(4):313–330. doi: 10.1093/oxfordjournals.molbev.a040503. [DOI] [PubMed] [Google Scholar]
  57. Li W. H., Wu C. I., Luo C. C. A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes. Mol Biol Evol. 1985 Mar;2(2):150–174. doi: 10.1093/oxfordjournals.molbev.a040343. [DOI] [PubMed] [Google Scholar]
  58. 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]
  59. McKinney R. E., Jr, Maha M. A., Connor E. M., Feinberg J., Scott G. B., Wulfsohn M., McIntosh K., Borkowsky W., Modlin J. F., Weintrub P. A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease. The Protocol 043 Study Group. N Engl J Med. 1991 Apr 11;324(15):1018–1025. doi: 10.1056/NEJM199104113241503. [DOI] [PubMed] [Google Scholar]
  60. Merrill J. E., Koyanagi Y., Zack J., Thomas L., Martin F., Chen I. S. Induction of interleukin-1 and tumor necrosis factor alpha in brain cultures by human immunodeficiency virus type 1. J Virol. 1992 Apr;66(4):2217–2225. doi: 10.1128/jvi.66.4.2217-2225.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Mervis R. J., Ahmad N., Lillehoj E. P., Raum M. G., Salazar F. H., Chan H. W., Venkatesan S. The gag gene products of human immunodeficiency virus type 1: alignment within the gag open reading frame, identification of posttranslational modifications, and evidence for alternative gag precursors. J Virol. 1988 Nov;62(11):3993–4002. doi: 10.1128/jvi.62.11.3993-4002.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. 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]
  63. Michael N. L., Vahey M., Burke D. S., Redfield R. R. Viral DNA and mRNA expression correlate with the stage of human immunodeficiency virus (HIV) type 1 infection in humans: evidence for viral replication in all stages of HIV disease. J Virol. 1992 Jan;66(1):310–316. doi: 10.1128/jvi.66.1.310-316.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Michaels J., Price R. W., Rosenblum M. K. Microglia in the giant cell encephalitis of acquired immune deficiency syndrome: proliferation, infection and fusion. Acta Neuropathol. 1988;76(4):373–379. doi: 10.1007/BF00686974. [DOI] [PubMed] [Google Scholar]
  65. Miedema F., Tersmette M., van Lier R. A. AIDS pathogenesis: a dynamic interaction between HIV and the immune system. Immunol Today. 1990 Aug;11(8):293–297. doi: 10.1016/0167-5699(90)90116-q. [DOI] [PubMed] [Google Scholar]
  66. Moore J. P., McKeating J. A., Huang Y. X., Ashkenazi A., Ho D. D. Virions of primary human immunodeficiency virus type 1 isolates resistant to soluble CD4 (sCD4) neutralization differ in sCD4 binding and glycoprotein gp120 retention from sCD4-sensitive isolates. J Virol. 1992 Jan;66(1):235–243. doi: 10.1128/jvi.66.1.235-243.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Muesing M. A., Smith D. H., Cabradilla C. D., Benton C. V., Lasky L. A., Capon D. J. Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus. Nature. 1985 Feb 7;313(6002):450–458. doi: 10.1038/313450a0. [DOI] [PubMed] [Google Scholar]
  68. Nabel G., Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16;326(6114):711–713. doi: 10.1038/326711a0. [DOI] [PubMed] [Google Scholar]
  69. 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]
  70. O'Brien W. A., Koyanagi Y., Namazie A., Zhao J. Q., Diagne A., Idler K., Zack J. A., Chen I. S. HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domain. Nature. 1990 Nov 1;348(6296):69–73. doi: 10.1038/348069a0. [DOI] [PubMed] [Google Scholar]
  71. Olshevsky U., Helseth E., Furman C., Li J., Haseltine W., Sodroski J. Identification of individual human immunodeficiency virus type 1 gp120 amino acids important for CD4 receptor binding. J Virol. 1990 Dec;64(12):5701–5707. doi: 10.1128/jvi.64.12.5701-5707.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Overbaugh J., Donahue P. R., Quackenbush S. L., Hoover E. A., Mullins J. I. Molecular cloning of a feline leukemia virus that induces fatal immunodeficiency disease in cats. Science. 1988 Feb 19;239(4842):906–910. doi: 10.1126/science.2893454. [DOI] [PubMed] [Google Scholar]
  73. Pang S., Koyanagi Y., Miles S., Wiley C., Vinters H. V., Chen I. S. High levels of unintegrated HIV-1 DNA in brain tissue of AIDS dementia patients. Nature. 1990 Jan 4;343(6253):85–89. doi: 10.1038/343085a0. [DOI] [PubMed] [Google Scholar]
  74. Pang S., Vinters H. V., Akashi T., O'Brien W. A., Chen I. S. HIV-1 env sequence variation in brain tissue of patients with AIDS-related neurologic disease. J Acquir Immune Defic Syndr. 1991;4(11):1082–1092. [PubMed] [Google Scholar]
  75. Pantaleo G., Graziosi C., Butini L., Pizzo P. A., Schnittman S. M., Kotler D. P., Fauci A. S. Lymphoid organs function as major reservoirs for human immunodeficiency virus. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9838–9842. doi: 10.1073/pnas.88.21.9838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Phillips R. E., Rowland-Jones S., Nixon D. F., Gotch F. M., Edwards J. P., Ogunlesi A. O., Elvin J. G., Rothbard J. A., Bangham C. R., Rizza C. R. Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature. 1991 Dec 12;354(6353):453–459. doi: 10.1038/354453a0. [DOI] [PubMed] [Google Scholar]
  77. Pizzo P. A., Eddy J., Falloon J., Balis F. M., Murphy R. F., Moss H., Wolters P., Brouwers P., Jarosinski P., Rubin M. Effect of continuous intravenous infusion of zidovudine (AZT) in children with symptomatic HIV infection. N Engl J Med. 1988 Oct 6;319(14):889–896. doi: 10.1056/NEJM198810063191401. [DOI] [PubMed] [Google Scholar]
  78. Ratner L., Haseltine W., Patarca R., Livak K. J., Starcich B., Josephs S. F., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeister K. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24;313(6000):277–284. doi: 10.1038/313277a0. [DOI] [PubMed] [Google Scholar]
  79. Rosen C. A., Sodroski J. G., Haseltine W. A. The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell. 1985 Jul;41(3):813–823. doi: 10.1016/s0092-8674(85)80062-3. [DOI] [PubMed] [Google Scholar]
  80. 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]
  81. Saag M. S., Hahn B. H., Gibbons J., Li Y., Parks E. S., Parks W. P., Shaw G. M. Extensive variation of human immunodeficiency virus type-1 in vivo. Nature. 1988 Aug 4;334(6181):440–444. doi: 10.1038/334440a0. [DOI] [PubMed] [Google Scholar]
  82. Saitou N., Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987 Jul;4(4):406–425. doi: 10.1093/oxfordjournals.molbev.a040454. [DOI] [PubMed] [Google Scholar]
  83. Sanchez-Pescador R., Power M. D., Barr P. J., Steimer K. S., Stempien M. M., Brown-Shimer S. L., Gee W. W., Renard A., Randolph A., Levy J. A. Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). Science. 1985 Feb 1;227(4686):484–492. doi: 10.1126/science.2578227. [DOI] [PubMed] [Google Scholar]
  84. Schnittman S. M., Greenhouse J. J., Psallidopoulos M. C., Baseler M., Salzman N. P., Fauci A. S., Lane H. C. Increasing viral burden in CD4+ T cells from patients with human immunodeficiency virus (HIV) infection reflects rapidly progressive immunosuppression and clinical disease. Ann Intern Med. 1990 Sep 15;113(6):438–443. doi: 10.7326/0003-4819-113-6-438. [DOI] [PubMed] [Google Scholar]
  85. Schnittman S. M., Psallidopoulos M. C., Lane H. C., Thompson L., Baseler M., Massari F., Fox C. H., Salzman N. P., Fauci A. S. The reservoir for HIV-1 in human peripheral blood is a T cell that maintains expression of CD4. Science. 1989 Jul 21;245(4915):305–308. doi: 10.1126/science.2665081. [DOI] [PubMed] [Google Scholar]
  86. 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]
  87. Schuitemaker H., Kootstra N. A., de Goede R. E., de Wolf F., Miedema F., Tersmette M. 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. J Virol. 1991 Jan;65(1):356–363. doi: 10.1128/jvi.65.1.356-363.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. 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]
  89. Shaw G. M., Hahn B. H., Arya S. K., Groopman J. E., Gallo R. C., Wong-Staal F. Molecular characterization of human T-cell leukemia (lymphotropic) virus type III in the acquired immune deficiency syndrome. Science. 1984 Dec 7;226(4679):1165–1171. doi: 10.1126/science.6095449. [DOI] [PubMed] [Google Scholar]
  90. Shaw G. M., Harper M. E., Hahn B. H., Epstein L. G., Gajdusek D. C., Price R. W., Navia B. A., Petito C. K., O'Hara C. J., Groopman J. E. HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science. 1985 Jan 11;227(4683):177–182. doi: 10.1126/science.2981429. [DOI] [PubMed] [Google Scholar]
  91. Shaw G. M., Levy P. C., LoBuglio A. F. Human lymphocyte, monocyte, and neutrophil antibody-dependent cell-mediated cytotoxicity toward human erythrocytes. Cell Immunol. 1978 Nov;41(1):122–133. doi: 10.1016/s0008-8749(78)80032-x. [DOI] [PubMed] [Google Scholar]
  92. Shaw G. M., Levy P. C., LoBuglio A. F. Human monocyte antibody-dependent cell-mediated cytotoxicity to tumor cells. J Clin Invest. 1978 Dec;62(6):1172–1180. doi: 10.1172/JCI109236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  93. Sidtis J. J., Price R. W. Early HIV-1 infection and the AIDS dementia complex. Neurology. 1990 Feb;40(2):323–326. doi: 10.1212/wnl.40.2.323. [DOI] [PubMed] [Google Scholar]
  94. Spencer D. C., Price R. W. Human immunodeficiency virus and the central nervous system. Annu Rev Microbiol. 1992;46:655–693. doi: 10.1146/annurev.mi.46.100192.003255. [DOI] [PubMed] [Google Scholar]
  95. Staden R. A new computer method for the storage and manipulation of DNA gel reading data. Nucleic Acids Res. 1980 Aug 25;8(16):3673–3694. doi: 10.1093/nar/8.16.3673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  96. 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]
  97. Stein D. S., Korvick J. A., Vermund S. H. CD4+ lymphocyte cell enumeration for prediction of clinical course of human immunodeficiency virus disease: a review. J Infect Dis. 1992 Feb;165(2):352–363. doi: 10.1093/infdis/165.2.352. [DOI] [PubMed] [Google Scholar]
  98. Strebel K., Klimkait T., Martin M. A. A novel gene of HIV-1, vpu, and its 16-kilodalton product. Science. 1988 Sep 2;241(4870):1221–1223. doi: 10.1126/science.3261888. [DOI] [PubMed] [Google Scholar]
  99. 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]
  100. Tersmette M., de Goede R. E., Al B. J., Winkel I. N., Gruters R. A., Cuypers H. T., Huisman H. G., Miedema F. Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. J Virol. 1988 Jun;62(6):2026–2032. doi: 10.1128/jvi.62.6.2026-2032.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  101. Thali M., Olshevsky U., Furman C., Gabuzda D., Li J., Sodroski J. Effects of changes in gp120-CD4 binding affinity on human immunodeficiency virus type 1 envelope glycoprotein function and soluble CD4 sensitivity. J Virol. 1991 Sep;65(9):5007–5012. doi: 10.1128/jvi.65.9.5007-5012.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  102. Vaishnav Y. N., Wong-Staal F. The biochemistry of AIDS. Annu Rev Biochem. 1991;60:577–630. doi: 10.1146/annurev.bi.60.070191.003045. [DOI] [PubMed] [Google Scholar]
  103. Vartanian J. P., Meyerhans A., Asjö B., Wain-Hobson S. Selection, recombination, and G----A hypermutation of human immunodeficiency virus type 1 genomes. J Virol. 1991 Apr;65(4):1779–1788. doi: 10.1128/jvi.65.4.1779-1788.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Veronese F. D., Copeland T. D., Oroszlan S., Gallo R. C., Sarngadharan M. G. Biochemical and immunological analysis of human immunodeficiency virus gag gene products p17 and p24. J Virol. 1988 Mar;62(3):795–801. doi: 10.1128/jvi.62.3.795-801.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  105. Volberding P. A., Lagakos S. W., Koch M. A., Pettinelli C., Myers M. W., Booth D. K., Balfour H. H., Jr, Reichman R. C., Bartlett J. A., Hirsch M. S. Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. N Engl J Med. 1990 Apr 5;322(14):941–949. doi: 10.1056/NEJM199004053221401. [DOI] [PubMed] [Google Scholar]
  106. Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M. Nucleotide sequence of the AIDS virus, LAV. Cell. 1985 Jan;40(1):9–17. doi: 10.1016/0092-8674(85)90303-4. [DOI] [PubMed] [Google Scholar]
  107. 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]
  108. Wong-Staal F., Shaw G. M., Hahn B. H., Salahuddin S. Z., Popovic M., Markham P., Redfield R., Gallo R. C. Genomic diversity of human T-lymphotropic virus type III (HTLV-III). Science. 1985 Aug 23;229(4715):759–762. doi: 10.1126/science.2992084. [DOI] [PubMed] [Google Scholar]

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