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J Virol. 1990 February; 64(2): 864–872.
PMCID: PMC249182

Human immunodeficiency virus-infected individuals contain provirus in small numbers of peripheral mononuclear cells and at low copy numbers.


In human immunodeficiency virus (HIV)-infected individuals, the proportion of circulating mononuclear cells (PBMCs) which carry HIV provirus and the number of HIV proviral sequences per infected PBMC have been matters for conjecture. Using a double polymerase chain reaction which allows the detection of single molecules of provirus and a method of quantifying the provirus molecules, we have measured provirus frequencies in infected individuals down to a level of one molecule per 10(6) PBMCs. As a general rule, only a small proportion of PBMCs contain provirus (median value of samples from 12 patients, one per 8,000 cells), and most if not all of the infected cells carry a single provirus molecule. The frequency of provirus-carrying cells correlated positively both with the progression of the disease and with the success with which virus could be isolated from the same patients by cocultivation methods. Of seven asymptomatic (Centers for Disease Control stage II) patients, all but one contained one provirus molecule per 6,000 to 80,000 cells; of five Centers for Disease Control stage IV patients, all but one contained one provirus molecule per 700 to 3,300 cells. When considered in conjunction with estimates of the frequency of PBMCs that express viral RNA, our results suggest that either (i) the majority of provirus-containing cells are monocytes or (ii) most provirus-containing lymphocytes are transcriptionally inactive. We also present nucleotide sequence data derived directly from provirus present in vivo which we show is not marred by the in vitro selection of potential virus variants or by errors introduced by Taq polymerase. We argue from these data that, of the provirus present in infected individuals, the proportion which is defective is not high in the regions sequenced.

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Selected References

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  • Allain JP, Laurian Y, Paul DA, Senn D. Serological markers in early stages of human immunodeficiency virus infection in haemophiliacs. Lancet. 1986 Nov 29;2(8518):1233–1236. [PubMed]
  • Andrews CA, Sullivan JL, Brettler DB, Brewster FE, Forsberg AD, Scesney S, Levine PH. Isolation of human immunodeficiency virus from hemophiliacs: correlation with clinical symptoms and immunologic abnormalities. J Pediatr. 1987 Nov;111(5):672–677. [PubMed]
  • Bell J, Ratner L. Specificity of polymerase chain amplification reactions for human immunodeficiency virus type 1 DNA sequences. AIDS Res Hum Retroviruses. 1989 Feb;5(1):87–95. [PubMed]
  • Folks TM, Powell D, Lightfoote M, Koenig S, Fauci AS, Benn S, Rabson A, Daugherty D, Gendelman HE, Hoggan MD, et al. Biological and biochemical characterization of a cloned Leu-3- cell surviving infection with the acquired immune deficiency syndrome retrovirus. J Exp Med. 1986 Jul 1;164(1):280–290. [PMC free article] [PubMed]
  • Gaines H, von Sydow M, Sönnerborg A, Albert J, Czajkowski J, Pehrson PO, Chiodi F, Moberg L, Fenyö EM, Asjö B, et al. Antibody response in primary human immunodeficiency virus infection. Lancet. 1987 May 30;1(8544):1249–1253. [PubMed]
  • Gartner S, Markovits P, Markovitz DM, Kaplan MH, Gallo RC, Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science. 1986 Jul 11;233(4760):215–219. [PubMed]
  • Goudsmit J, de Wolf F, Paul DA, Epstein LG, Lange JM, Krone WJ, Speelman H, Wolters EC, Van der Noordaa J, Oleske JM, et al. Expression of human immunodeficiency virus antigen (HIV-Ag) in serum and cerebrospinal fluid during acute and chronic infection. Lancet. 1986 Jul 26;2(8500):177–180. [PubMed]
  • Hahn BH, Shaw GM, Taylor ME, Redfield RR, Markham PD, Salahuddin SZ, Wong-Staal F, Gallo RC, Parks ES, Parks WP. 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. [PubMed]
  • Harper ME, Marselle LM, Gallo RC, Wong-Staal F. Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc Natl Acad Sci U S A. 1986 Feb;83(3):772–776. [PubMed]
  • Hart C, Schochetman G, Spira T, Lifson A, Moore J, Galphin J, Sninsky J, Ou CY. Direct detection of HIV RNA expression in seropositive subjects. Lancet. 1988 Sep 10;2(8611):596–599. [PubMed]
  • Ho DD, Rota TR, Hirsch MS. Infection of monocyte/macrophages by human T lymphotropic virus type III. J Clin Invest. 1986 May;77(5):1712–1715. [PMC free article] [PubMed]
  • Hoxie JA, Haggarty BS, Rackowski JL, Pillsbury N, Levy JA. Persistent noncytopathic infection of normal human T lymphocytes with AIDS-associated retrovirus. Science. 1985 Sep 27;229(4720):1400–1402. [PubMed]
  • Kwok S, Mack DH, Mullis KB, Poiesz B, Ehrlich G, Blair D, Friedman-Kien A, Sninsky JJ. Identification of human immunodeficiency virus sequences by using in vitro enzymatic amplification and oligomer cleavage detection. J Virol. 1987 May;61(5):1690–1694. [PMC free article] [PubMed]
  • Lee JJ, Costlow NA. A molecular titration assay to measure transcript prevalence levels. Methods Enzymol. 1987;152:633–648. [PubMed]
  • Brown AL, Monaghan P. Evolution of the structural proteins of human immunodeficiency virus: selective constraints on nucleotide substitution. AIDS Res Hum Retroviruses. 1988 Dec;4(6):399–407. [PubMed]
  • Lo YM, Mehal WZ, Fleming KA. False-positive results and the polymerase chain reaction. Lancet. 1988 Sep 17;2(8612):679–679. [PubMed]
  • Ludlam CA, Tucker J, Steel CM, Tedder RS, Cheingsong-Popov R, Weiss RA, McClelland DB, Philp I, Prescott RJ. Human T-lymphotropic virus type III (HTLV-III) infection in seronegative haemophiliacs after transfusion of factor VIII. Lancet. 1985 Aug 3;2(8449):233–236. [PubMed]
  • Mullis KB, Faloona FA. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335–350. [PubMed]
  • Nicholson JK, Cross GD, Callaway CS, McDougal JS. In vitro infection of human monocytes with human T lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). J Immunol. 1986 Jul 1;137(1):323–329. [PubMed]
  • Ou CY, Kwok S, Mitchell SW, Mack DH, Sninsky JJ, Krebs JW, Feorino P, Warfield D, Schochetman G. DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science. 1988 Jan 15;239(4837):295–297. [PubMed]
  • Paul DA, Falk LA, Kessler HA, Chase RM, Blaauw B, Chudwin DS, Landay AL. Correlation of serum HIV antigen and antibody with clinical status in HIV-infected patients. J Med Virol. 1987 Aug;22(4):357–363. [PubMed]
  • Plata F, Autran B, Martins LP, Wain-Hobson S, Raphaël M, Mayaud C, Denis M, Guillon JM, Debré P. AIDS virus-specific cytotoxic T lymphocytes in lung disorders. Nature. 1987 Jul 23;328(6128):348–351. [PubMed]
  • Richman DD, McCutchan JA, Spector SA. Detecting human immunodeficiency virus RNA in peripheral blood mononuclear cells by nucleic acid hybridization. J Infect Dis. 1987 Nov;156(5):823–827. [PubMed]
  • Saag MS, Hahn BH, Gibbons J, Li Y, Parks ES, Parks WP, Shaw GM. Extensive variation of human immunodeficiency virus type-1 in vivo. Nature. 1988 Aug 4;334(6181):440–444. [PubMed]
  • Salahuddin SZ, Markham PD, Popovic M, Sarngadharan MG, Orndorff S, Fladagar A, Patel A, Gold J, Gallo RC. Isolation of infectious human T-cell leukemia/lymphotropic virus type III (HTLV-III) from patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) and from healthy carriers: a study of risk groups and tissue sources. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5530–5534. [PubMed]
  • Salahuddin SZ, Rose RM, Groopman JE, Markham PD, Gallo RC. Human T lymphotropic virus type III infection of human alveolar macrophages. Blood. 1986 Jul;68(1):281–284. [PubMed]
  • Schnittman SM, Psallidopoulos MC, Lane HC, Thompson L, Baseler M, Massari F, Fox CH, Salzman NP, Fauci AS. 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. [PubMed]
  • Shaw GM, Hahn BH, Arya SK, Groopman JE, Gallo RC, 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. [PubMed]
  • Shaw GM, Harper ME, Hahn BH, Epstein LG, Gajdusek DC, Price RW, Navia BA, Petito CK, O'Hara CJ, Groopman JE, et al. HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science. 1985 Jan 11;227(4683):177–182. [PubMed]
  • Starcich BR, Hahn BH, Shaw GM, McNeely PD, Modrow S, Wolf H, Parks ES, Parks WP, Josephs SF, Gallo RC, et al. 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. [PubMed]
  • Tindall KR, Kunkel TA. Fidelity of DNA synthesis by the Thermus aquaticus DNA polymerase. Biochemistry. 1988 Aug 9;27(16):6008–6013. [PubMed]
  • Ulrich PP, Busch MP, el-Beik T, Shiota J, Vennari J, Shriver K, Vyas GN. Assessment of human immunodeficiency virus expression in cocultures of peripheral blood mononuclear cells from healthy seropositive subjects. J Med Virol. 1988 May;25(1):1–10. [PubMed]
  • Zagury D, Bernard J, Leonard R, Cheynier R, Feldman M, Sarin PS, Gallo RC. Long-term cultures of HTLV-III--infected T cells: a model of cytopathology of T-cell depletion in AIDS. Science. 1986 Feb 21;231(4740):850–853. [PubMed]

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