Abstract
To determine whether the biological variability of HIV-1 has any clinical significance, the highly variable cytopathogenicity of 153 HIV-1 strains, isolated from 119 hemophiliacs, was related to the number of CD4+ lymphocytes present in the patient's blood at the time of virus isolation. It was shown that the cytopathogenicity of the HIV-1 isolates was inversely correlated with the number of CD4+ lymphocytes. The highest CD4+ cell numbers were observed in 34 latently infected patients characterized by HIV seropositivity, failure of virus isolation, and detection of viral DNA by the polymerase chain reaction. Cytopathogenicity of the HIV-1 isolates was a reliable prognostic marker and correlated well with other lesssensitive prognostic parameters, including the detection of infectious virus and p24 antigen in the plasma, and the decline of p24 antibody in the serum. The results suggest that the viral isolates — if not subjected to extensive passage — represent in vivo variants selected from a heterogeneous viral population according to the particular immunological conditions of the host.
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References
Anand R, Reed C, Forlenza S, Siegal F, Cheung T, Moore J (1987) Non-cytocidal natural variants of human immunodeficiency virus isolated from AIDS patients with neurological disorders. Lancet I:234–238
Andrews CA, Sullivan JL, Brettler DB, Brewster FE, Forsberg AD, Scesney S, Levine PH (1987) Isolation of human immunodeficiency virus from hemophiliacs: correlation with clinical symptoms and immunological abnormalities. J Pediatr 111:672–677
Briesen H, Becker WB, Henco K, Helm EB, Gelderblom HR, Brede HD, Rübsamen-Waigmann H (1987) Isolation frequency and growth properties of HIV-variants: multiple simultaneous variants in a patient demonstrated by molecular cloning. J Med Virol 23:51–66
Cheng-Mayer C, Seto D, Tateno M, Levy JA (1988) Biological features of HIV-1 that correlate with virulence in the host. Science 240:80–82
Coombs RW, Collier AC, Allain JP, Nikora B, Leuther M, Gjerset GF, Corey L (1989) Plasma viremia in human immunodeficiency virus infection. N Engl J Med 321:1626–1631
Ehrnst A, Sönnerborg A, Bergdahl S, Strånnegard Ö (1988) Efficient isolation of HIV from plasma during different stages of HIV infection. J Med Virol 26:23–32
Evans LA, McHugh TM, Stiles DP, Levy JA (1987) Differential ability of human immunodeficiency virus isolates to productively infect human cells. J Immunol 138:3415–3418
Fisher GA, Ensoli B, Looney D, Rose A, Gallo RC, Saag MS, Shaw GM, Hahn BH, Wong-Staal F (1988) Biologically diverse molecular variants within a single HIV-1 isolate. Nature 334:444–447
Goedert JJ, Kessler CM, Aledort LM, Biggar RJ, Andes A, Gilbert CW, Drummond JE, Vaidya K, Mann DL, Eyster E, Ragni MV, Lederman MM, Cohen AR, Bray GL, Rosenberg PS, Friedman RM, Hilgartner MW, Blattner WA, Kroner B, Gail MH (1989) A prospective study of human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia. N Engl J Med 321:1141–1148
Goodenow M, Huet T, Saurin W, Kwok S, Sninsky J, Wain-Hobson S (1989) HIV-1 isolates are rapidly evolving quasispecies: evidence for viral mixtures and preferred nucleotide substitutions. J AIDS 2:344–352
Ho DH, Moudgil MS, Masud Alam MS (1989) Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N Engl J Med 321:1621–1625
Jackson JB, Sannerud KJ, Hopsicker JS, Kwok SY, Edson JR, Balfour HH (1988) Hemophiliacs with HIV antibody are actively infected. JAMA 260:2236–2239
Kamradt T, Niese D, Schneweis KE, Brackmann HH, Kamps B, Loo B, Hammerstein U (1989) Natural history of HIV-infection in hemophiliacs: clinical, immunological, and virological findings. Klin Wochenschr 67:1033–1041
Lange J, Goudsmit J (1987) Decline of antibody reactivity to HIV core protein secondary to increased production of HIV antigen. Lancet I:448
Lange JMA, Paul DA, Huisman HG, de Wolf F, van den Berg H, Coutinho RA, Danner SA, van der Noordaa J, Goudsmit J (1986) Persistent HIV antigenaemia and decline of HIV core antibodies associated with transition to AIDS. Br Med J 293:1459–1462
Leonard R, Zagury D, Desportes I, Bernard J, Zagury JF, Gallo RC (1988) Cytopathic effect of human immunodeficiency virus in T4 cells linked to the last stage of virus infection. Proc Natl Acad Sci USA 85:3570–3574
Ou CY, Kwok S, Mitchell SW, Mack DH, Sninsky J, Krebs JW, Feorino P, Warfield D, Schochetman G (1988) DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science 239:295–297
Psallidopoulos MC, Schnittman SM, Thompson LM, Baseler M, Fauci AS, Lane HC, Salzman NP (1989) Integrated proviral human immunodeficiency virus type 1 is present in CD4+ peripheral blood lymphocytes in healthy seropositive individuals. J Virol 63:4626–4631
Rübsamen-Waigmann H, Becker WB, Helm EB, Brodt R, Fischer H, Henco K, Brede HD (1986) Isolation of variants of lymphocytopathic retroviruses from the peripheral blood and cerebrospinal fluid of patients with ARC or AIDS. J Med Virol 19:335–344
Saag MS, Hahn BH, Gibbons J, Li Y, Parks ES, Parks WP, Shaw GM (1988) Extensive variation of human immunodeficiency virus type 1 in vivo. Nature 334:440–444
Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA (1988) Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–491
Sakai K, Dewhurst S, Ma X, Volsky DJ (1988) Differences in cytopathogenicity and host cell range among infectious molecular clones of human immunodeficiency virus type 1 simultaneously isolated from an individual. J Virol 62:4078–4085
Schneweis KE, Ackermann A, Friedrich A, Kleim JP, Kornau K, Ruff R, Siefer-Wippermann B (1989) Comparison of different methods for detecting human immune deficiency virus in human immunodeficiency virus-seropositive hemophiliacs. J Med Virol 29:94–101
Schnittman SM, Psallidopoulos MC, Lane HC, Thompson L, Baseler M, Massari F, Fox CH, Salzman NP, Fauci AS (1989) The reservoir for HIV-1 in human peripheral blood is a T cell that maintains expression of CD4. Science 245:305–308
Tersmette M, de Goede REY, Al BJM, Winkel IN, Gruters RA, Cuypers HT, Hisman HG, Miedema F (1988) 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 62:2026–2032
Tersmette M, Gruters RA, de Wolf F, de Goede REY, Lange JMA, Schellekens PTA, Goudsmit J, Huisman HG, Miedema F (1989) 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 63:2118–2125
Weiss RA, Clapham PR, Weber JN, Dalgleish AG, Lasky LA, Berman PW (1986) Variable and conserved neutralization antigens of human immunodeficiency virus. Nature 324:572–575
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Schneweis, K.E., Kleim, JP., Bailly, E. et al. Graded cytopathogenicity of the human immunodeficiency virus (HIV) in the course of HIV infection. Med Microbiol Immunol 179, 193–203 (1990). https://doi.org/10.1007/BF00195250
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DOI: https://doi.org/10.1007/BF00195250