Understanding the basis of CD4+ T-cell depletion in macaques infected by a simian-human immunodeficiency virus

Bijan Etemad-Moghadam, Daniela Rhone, Tavis Steenbeke, Ying Sun, Judith Manola, Rebecca Gelman, John W. Fanton, Paul Racz, Klara Tenner-Racz, Michael Axthelm, Norman L. Letvin, Joseph Sodroski

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    Abstract

    The efficacy of candidate AIDS vaccines to mediate protection against viral infection and pathogenesis is evaluated, at a preclinical stage, in animal models. One model that is favored because the infecting virus is closely related to HIV-1 and because of the rapidity of pathogenic outcomes is the infection of Old World monkeys by simian-human immunodeficiency virus (SHIV) chimerae. We investigated the basis for the depletion of CD4+ T lymphocytes in a SHIV-macaque model. Molecularly cloned SHIVs, SHIV-89.6 and SHIV-KB9, differ in the ability to cause CD4+ T-cell loss at a given level of virus replication in monkeys. The envelope glycoproteins of the pathogenic SHIV-KB9 mediate membrane-fusion in cultured T lymphocytes more efficiently than the envelope glycoproteins of the non-pathogenic SHIV-89.6. The minimal envelope glycoprotein region that specifies this increase in membrane-fusing capacity was sufficient to convert SHIV-89.6 into a virus that causes profound CD4+ T-cell depletion in monkeys. Conversely, two single amino acid changes that decrease the membrane-fusing ability of the SHIV-KB9 envelope glycoproteins also attenuated the CD4+ T-cell destruction that accompanied a given level of virus replication in SHIV-infected monkeys. Thus, the ability of the HIV-1 envelope glycoproteins to fuse membranes, which has been implicated in the induction of viral cytopathic effects in vitro, contributes to the capacity of the pathogenic SHIV to deplete CD4+ T lymphocytes in vivo.

    Original languageEnglish (US)
    Pages (from-to)1934-1937
    Number of pages4
    JournalVaccine
    Volume20
    Issue number15
    DOIs
    StatePublished - May 6 2002

    Fingerprint

    Simian Immunodeficiency Virus
    Human immunodeficiency virus
    Macaca
    T-lymphocytes
    HIV
    T-Lymphocytes
    glycoproteins
    Glycoproteins
    Haplorhini
    monkeys
    Virus Replication
    virus replication
    Human immunodeficiency virus 1
    Membranes
    HIV-1
    Viral Cytopathogenic Effect
    Cercopithecidae
    Viruses
    AIDS Vaccines
    viruses

    Keywords

    • CD4 T-cell depletion
    • Membrane fusion
    • Simian-human immunodeficiency virus

    ASJC Scopus subject areas

    • Immunology
    • Microbiology
    • Virology
    • Infectious Diseases
    • Public Health, Environmental and Occupational Health
    • veterinary(all)

    Cite this

    Etemad-Moghadam, B., Rhone, D., Steenbeke, T., Sun, Y., Manola, J., Gelman, R., ... Sodroski, J. (2002). Understanding the basis of CD4+ T-cell depletion in macaques infected by a simian-human immunodeficiency virus. Vaccine, 20(15), 1934-1937. https://doi.org/10.1016/S0264-410X(02)00072-5

    Understanding the basis of CD4+ T-cell depletion in macaques infected by a simian-human immunodeficiency virus. / Etemad-Moghadam, Bijan; Rhone, Daniela; Steenbeke, Tavis; Sun, Ying; Manola, Judith; Gelman, Rebecca; Fanton, John W.; Racz, Paul; Tenner-Racz, Klara; Axthelm, Michael; Letvin, Norman L.; Sodroski, Joseph.

    In: Vaccine, Vol. 20, No. 15, 06.05.2002, p. 1934-1937.

    Research output: Contribution to journalArticle

    Etemad-Moghadam, B, Rhone, D, Steenbeke, T, Sun, Y, Manola, J, Gelman, R, Fanton, JW, Racz, P, Tenner-Racz, K, Axthelm, M, Letvin, NL & Sodroski, J 2002, 'Understanding the basis of CD4+ T-cell depletion in macaques infected by a simian-human immunodeficiency virus', Vaccine, vol. 20, no. 15, pp. 1934-1937. https://doi.org/10.1016/S0264-410X(02)00072-5
    Etemad-Moghadam, Bijan ; Rhone, Daniela ; Steenbeke, Tavis ; Sun, Ying ; Manola, Judith ; Gelman, Rebecca ; Fanton, John W. ; Racz, Paul ; Tenner-Racz, Klara ; Axthelm, Michael ; Letvin, Norman L. ; Sodroski, Joseph. / Understanding the basis of CD4+ T-cell depletion in macaques infected by a simian-human immunodeficiency virus. In: Vaccine. 2002 ; Vol. 20, No. 15. pp. 1934-1937.
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    abstract = "The efficacy of candidate AIDS vaccines to mediate protection against viral infection and pathogenesis is evaluated, at a preclinical stage, in animal models. One model that is favored because the infecting virus is closely related to HIV-1 and because of the rapidity of pathogenic outcomes is the infection of Old World monkeys by simian-human immunodeficiency virus (SHIV) chimerae. We investigated the basis for the depletion of CD4+ T lymphocytes in a SHIV-macaque model. Molecularly cloned SHIVs, SHIV-89.6 and SHIV-KB9, differ in the ability to cause CD4+ T-cell loss at a given level of virus replication in monkeys. The envelope glycoproteins of the pathogenic SHIV-KB9 mediate membrane-fusion in cultured T lymphocytes more efficiently than the envelope glycoproteins of the non-pathogenic SHIV-89.6. The minimal envelope glycoprotein region that specifies this increase in membrane-fusing capacity was sufficient to convert SHIV-89.6 into a virus that causes profound CD4+ T-cell depletion in monkeys. Conversely, two single amino acid changes that decrease the membrane-fusing ability of the SHIV-KB9 envelope glycoproteins also attenuated the CD4+ T-cell destruction that accompanied a given level of virus replication in SHIV-infected monkeys. Thus, the ability of the HIV-1 envelope glycoproteins to fuse membranes, which has been implicated in the induction of viral cytopathic effects in vitro, contributes to the capacity of the pathogenic SHIV to deplete CD4+ T lymphocytes in vivo.",
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