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. 1991 Aug;65(8):3973–3985. doi: 10.1128/jvi.65.8.3973-3985.1991

Molecular characterization of human immunodeficiency virus type 1 cloned directly from uncultured human brain tissue: identification of replication-competent and -defective viral genomes.

Y Li 1, J C Kappes 1, J A Conway 1, R W Price 1, G M Shaw 1, B H Hahn 1
PMCID: PMC248827  PMID: 1830110

Abstract

All presently available replication-competent proviral clones of human immunodeficiency virus type 1 (HIV-1) are derived from cell culture-amplified virus. Since tissue culture is highly selective for viral strains with an in vitro growth advantage, such clones may not be representative of the biologically relevant virus present in vivo. In this study, we report the molecular cloning and genotypic characterization of 10 HIV-1 genomes directly from uncultured brain tissue of a patient with AIDS dementia complex. Targeting unintegrated circular HIV-1 molecules for recombinant lambda phage cloning, we obtained four full-length genomes with one or two long terminal repeats (LTRs), three defective genomes with internal deletions, two rearranged genomes with inverted LTR sequences, and one integrated proviral half with flanking cellular sequences. Nucleotide sequence analysis of these clones demonstrated chromosomal integration, circle formation, genomic inversion, and LTR-mediated autointegration of HIV-1 genomes in vivo. Comparison of a 510-bp hypervariable envelope region among 8 lambda phage-derived and 12 polymerase chain reaction-derived clones from the same brain specimen identified a predominant viral form as well as genetically divergent variants. Variability among 19 of 20 clones ranged between 0.2 and 1.2%. One clone exhibited 8.2% nucleotide sequence differences consisting almost exclusively of G-to-A changes. Transfection of the four full-length HIV-1 genomes identified one clone (YU-2) as replication competent and exhibiting growth characteristics similar to those of tissue culture-derived macrophage tropic strains of HIV-1. These results demonstrate, for the first time, that replication-competent HIV-1 genomes, complex mixtures of defective viral forms, and chromosomally integrated provirus persist in vivo. In addition, the brain-derived viral clones are expected to prove valuable for future studies of macrophage and neurotropism as well as for the analysis of other viral properties that are subject to in vitro selection pressures.

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Selected References

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  1. 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]
  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. Bernstein D. I., Stanberry L. R., Harrison C. J., Kappes J. C., Myers M. G. Antibody response, recurrence patterns and subsequent herpes simplex virus type 2 (HSV-2) re-infection following initial HSV-2 infection of guinea-pigs: effects of acyclovir. J Gen Virol. 1986 Aug;67(Pt 8):1601–1612. doi: 10.1099/0022-1317-67-8-1601. [DOI] [PubMed] [Google Scholar]
  4. Budka H. Multinucleated giant cells in brain: a hallmark of the acquired immune deficiency syndrome (AIDS). Acta Neuropathol. 1986;69(3-4):253–258. doi: 10.1007/BF00688301. [DOI] [PubMed] [Google Scholar]
  5. Bushman F. D., Fujiwara T., Craigie R. Retroviral DNA integration directed by HIV integration protein in vitro. Science. 1990 Sep 28;249(4976):1555–1558. doi: 10.1126/science.2171144. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Cheng-Mayer C., Weiss C., Seto D., Levy J. A. Isolates of human immunodeficiency virus type 1 from the brain may constitute a special group of the AIDS virus. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8575–8579. doi: 10.1073/pnas.86.21.8575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Epstein L. G., Sharer L. R., Joshi V. V., Fojas M. M., Koenigsberger M. R., Oleske J. M. Progressive encephalopathy in children with acquired immune deficiency syndrome. Ann Neurol. 1985 May;17(5):488–496. doi: 10.1002/ana.410170512. [DOI] [PubMed] [Google Scholar]
  11. Evans L. A., McHugh T. M., Stites D. P., Levy J. A. Differential ability of human immunodeficiency virus isolates to productively infect human cells. J Immunol. 1987 May 15;138(10):3415–3418. [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. 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]
  15. 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]
  16. Gelderblom H. R., Hausmann E. H., Ozel M., Pauli G., Koch M. A. Fine structure of human immunodeficiency virus (HIV) and immunolocalization of structural proteins. Virology. 1987 Jan;156(1):171–176. doi: 10.1016/0042-6822(87)90449-1. [DOI] [PubMed] [Google Scholar]
  17. Giulian D., Vaca K., Noonan C. A. Secretion of neurotoxins by mononuclear phagocytes infected with HIV-1. Science. 1990 Dec 14;250(4987):1593–1596. doi: 10.1126/science.2148832. [DOI] [PubMed] [Google Scholar]
  18. Goff S. P. Integration of retroviral DNA into the genome of the infected cell. Cancer Cells. 1990 Jun;2(6):172–178. [PubMed] [Google Scholar]
  19. 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]
  20. Gyorkey F., Melnick J. L., Gyorkey P. Human immunodeficiency virus in brain biopsies of patients with AIDS and progressive encephalopathy. J Infect Dis. 1987 May;155(5):870–876. doi: 10.1093/infdis/155.5.870. [DOI] [PubMed] [Google Scholar]
  21. Hahn B. H., Shaw G. M., Arya S. K., Popovic M., Gallo R. C., Wong-Staal F. Molecular cloning and characterization of the HTLV-III virus associated with AIDS. Nature. 1984 Nov 8;312(5990):166–169. doi: 10.1038/312166a0. [DOI] [PubMed] [Google Scholar]
  22. Harris J. D., Blum H., Scott J., Traynor B., Ventura P., Haase A. Slow virus visna: reproduction in vitro of virus from extrachromosomal DNA. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7212–7215. doi: 10.1073/pnas.81.22.7212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ho D. D., Rota T. R., Schooley R. T., Kaplan J. C., Allan J. D., Groopman J. E., Resnick L., Felsenstein D., Andrews C. A., Hirsch M. S. Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med. 1985 Dec 12;313(24):1493–1497. doi: 10.1056/NEJM198512123132401. [DOI] [PubMed] [Google Scholar]
  24. Hong T., Drlica K., Pinter A., Murphy E. Circular DNA of human immunodeficiency virus: analysis of circle junction nucleotide sequences. J Virol. 1991 Jan;65(1):551–555. doi: 10.1128/jvi.65.1.551-555.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kato T., Hirano A., Llena J. F., Dembitzer H. M. Neuropathology of acquired immune deficiency syndrome (AIDS) in 53 autopsy cases with particular emphasis on microglial nodules and multinucleated giant cells. Acta Neuropathol. 1987;73(3):287–294. doi: 10.1007/BF00686624. [DOI] [PubMed] [Google Scholar]
  26. Kikukawa R., Koyanagi Y., Harada S., Kobayashi N., Hatanaka M., Yamamoto N. Differential susceptibility to the acquired immunodeficiency syndrome retrovirus in cloned cells of human leukemic T-cell line Molt-4. J Virol. 1986 Mar;57(3):1159–1162. doi: 10.1128/jvi.57.3.1159-1162.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Koenig S., Gendelman H. E., Orenstein J. M., Dal Canto M. C., Pezeshkpour G. H., Yungbluth M., Janotta F., Aksamit A., Martin M. A., Fauci A. S. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science. 1986 Sep 5;233(4768):1089–1093. doi: 10.1126/science.3016903. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Kulkosky J., Skalka A. M. HIV DNA integration: observations and interferences. J Acquir Immune Defic Syndr. 1990;3(9):839–851. [PubMed] [Google Scholar]
  30. 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]
  31. Levy J. A., Shimabukuro J., Hollander H., Mills J., Kaminsky L. Isolation of AIDS-associated retroviruses from cerebrospinal fluid and brain of patients with neurological symptoms. Lancet. 1985 Sep 14;2(8455):586–588. [PubMed] [Google Scholar]
  32. Liu Z. Q., Wood C., Levy J. A., Cheng-Mayer C. The viral envelope gene is involved in macrophage tropism of a human immunodeficiency virus type 1 strain isolated from brain tissue. J Virol. 1990 Dec;64(12):6148–6153. doi: 10.1128/jvi.64.12.6148-6153.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Meyenhofer M. F., Epstein L. G., Cho E. S., Sharer L. R. Ultrastructural morphology and intracellular production of human immunodeficiency virus (HIV) in brain. J Neuropathol Exp Neurol. 1987 Jul;46(4):474–484. doi: 10.1097/00005072-198707000-00006. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. 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]
  37. 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]
  38. Olsen J. C., Bova-Hill C., Grandgenett D. P., Quinn T. P., Manfredi J. P., Swanstrom R. Rearrangements in unintegrated retroviral DNA are complex and are the result of multiple genetic determinants. J Virol. 1990 Nov;64(11):5475–5484. doi: 10.1128/jvi.64.11.5475-5484.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Pathak V. K., Temin H. M. Broad spectrum of in vivo forward mutations, hypermutations, and mutational hotspots in a retroviral shuttle vector after a single replication cycle: substitutions, frameshifts, and hypermutations. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6019–6023. doi: 10.1073/pnas.87.16.6019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Pauza C. D., Galindo J. Persistent human immunodeficiency virus type 1 infection of monoblastoid cells leads to accumulation of self-integrated viral DNA and to production of defective virions. J Virol. 1989 Sep;63(9):3700–3707. doi: 10.1128/jvi.63.9.3700-3707.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Pauza C. D. Two bases are deleted from the termini of HIV-1 linear DNA during integrative recombination. Virology. 1990 Dec;179(2):886–889. doi: 10.1016/0042-6822(90)90161-j. [DOI] [PubMed] [Google Scholar]
  43. Price R. W., Brew B. J., Rosenblum M. The AIDS dementia complex and HIV-1 brain infection: a pathogenetic model of virus-immune interaction. Res Publ Assoc Res Nerv Ment Dis. 1990;68:269–290. [PubMed] [Google Scholar]
  44. Price R. W., Brew B., Sidtis J., Rosenblum M., Scheck A. C., Cleary P. The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science. 1988 Feb 5;239(4840):586–592. doi: 10.1126/science.3277272. [DOI] [PubMed] [Google Scholar]
  45. Ratner L., Fisher A., Jagodzinski L. L., Mitsuya H., Liou R. S., Gallo R. C., Wong-Staal F. Complete nucleotide sequences of functional clones of the AIDS virus. AIDS Res Hum Retroviruses. 1987 Spring;3(1):57–69. doi: 10.1089/aid.1987.3.57. [DOI] [PubMed] [Google Scholar]
  46. 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]
  47. Salter R. D., Howell D. N., Cresswell P. Genes regulating HLA class I antigen expression in T-B lymphoblast hybrids. Immunogenetics. 1985;21(3):235–246. doi: 10.1007/BF00375376. [DOI] [PubMed] [Google Scholar]
  48. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Sharer L. R., Cho E. S., Epstein L. G. Multinucleated giant cells and HTLV-III in AIDS encephalopathy. Hum Pathol. 1985 Aug;16(8):760–760. doi: 10.1016/s0046-8177(85)80245-8. [DOI] [PubMed] [Google Scholar]
  50. 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]
  51. 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]
  52. 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]
  53. Shoemaker C., Goff S., Gilboa E., Paskind M., Mitra S. W., Baltimore D. Structure of a cloned circular Moloney murine leukemia virus DNA molecule containing an inverted segment: implications for retrovirus integration. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3932–3936. doi: 10.1073/pnas.77.7.3932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Shoemaker C., Hoffman J., Goff S. P., Baltimore D. Intramolecular integration within Moloney murine leukemia virus DNA. J Virol. 1981 Oct;40(1):164–172. doi: 10.1128/jvi.40.1.164-172.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Smith J. S., Kim S. Y., Roth M. J. Analysis of long terminal repeat circle junctions of human immunodeficiency virus type 1. J Virol. 1990 Dec;64(12):6286–6290. doi: 10.1128/jvi.64.12.6286-6290.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Smith S. D., Shatsky M., Cohen P. S., Warnke R., Link M. P., Glader B. E. Monoclonal antibody and enzymatic profiles of human malignant T-lymphoid cells and derived cell lines. Cancer Res. 1984 Dec;44(12 Pt 1):5657–5660. [PubMed] [Google Scholar]
  57. Tamura T., Takano T. Long terminal repeat (LTR)-derived recombination of retroviral DNA: sequence analyses of an aberrant clone of baboon endogenous virus DNA which carries an inversion from the LTR to the gag region. Nucleic Acids Res. 1982 Sep 11;10(17):5333–5343. doi: 10.1093/nar/10.17.5333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. 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]
  59. Van Beveren C., Rands E., Chattopadhyay S. K., Lowy D. R., Verma I. M. Long terminal repeat of murine retroviral DNAs: sequence analysis, host-proviral junctions, and preintegration site. J Virol. 1982 Feb;41(2):542–556. doi: 10.1128/jvi.41.2.542-556.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. 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]
  61. Vazeux R., Brousse N., Jarry A., Henin D., Marche C., Vedrenne C., Mikol J., Wolff M., Michon C., Rozenbaum W. AIDS subacute encephalitis. Identification of HIV-infected cells. Am J Pathol. 1987 Mar;126(3):403–410. [PMC free article] [PubMed] [Google Scholar]
  62. Vink C., Groenink M., Elgersma Y., Fouchier R. A., Tersmette M., Plasterk R. H. Analysis of the junctions between human immunodeficiency virus type 1 proviral DNA and human DNA. J Virol. 1990 Nov;64(11):5626–5627. doi: 10.1128/jvi.64.11.5626-5627.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Watkins B. A., Dorn H. H., Kelly W. B., Armstrong R. C., Potts B. J., Michaels F., Kufta C. V., Dubois-Dalcq M. Specific tropism of HIV-1 for microglial cells in primary human brain cultures. Science. 1990 Aug 3;249(4968):549–553. doi: 10.1126/science.2200125. [DOI] [PubMed] [Google Scholar]
  64. Westervelt P., Gendelman H. E., Ratner L. Identification of a determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3097–3101. doi: 10.1073/pnas.88.8.3097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Whitcomb J. M., Kumar R., Hughes S. H. Sequence of the circle junction of human immunodeficiency virus type 1: implications for reverse transcription and integration. J Virol. 1990 Oct;64(10):4903–4906. doi: 10.1128/jvi.64.10.4903-4906.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Wiley C. A., Schrier R. D., Nelson J. A., Lampert P. W., Oldstone M. B. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7089–7093. doi: 10.1073/pnas.83.18.7089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. York-Higgins D., Cheng-Mayer C., Bauer D., Levy J. A., Dina D. Human immunodeficiency virus type 1 cellular host range, replication, and cytopathicity are linked to the envelope region of the viral genome. J Virol. 1990 Aug;64(8):4016–4020. doi: 10.1128/jvi.64.8.4016-4020.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]

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