Infection by HIV-1 causes persistent, long-term high virus production in macrophages. Major evidence, both in humans and in primate models, shows the crucial role of macrophages in sustaining virus production and in mediating a cytopathic effect on bystander CD4+ T lymphocytes and neuronal cells. In the present study, we used severe combined immunodeficient (SCID) mice engrafted with human peripheral blood lymphocytes (hu-PBL-SCID mice) to investigate the in vivo effect of HIV-1-infected macrophages on virus spread and CD4+ T lymphocyte depletion, and the ability of a mAb against nerve growth factor (NGF, a neurokine essential for the survival of HIV-1-infected macrophages) to suppress the pathogenetic events mediated by infected macrophages. Injection of mice with as few as 500 HIV-exposed macrophages causes (i) complete depletion of several millions of autologous CD4+ T lymphocytes, (ii) sustained HIV viremia, and (iii) spreading of HIV-1 DNA in mouse lymphoid organs. In contrast, in vivo treatment with an anti-NGF Ab completely abrogates all effects mediated by HIV-infected macrophages. Taken together, the results demonstrate the remarkable power of macrophages in sustaining in vivo HIV-1 infection, and that such a phenomenon can be specifically abrogated by an anti-NGF Ab. This may open new perspectives of experimental approaches aimed at selectively eliminating persistently infected macrophages from the bodies of HIV-infected patients.

Garaci, E., Aquaro, S., Lapenta, C., Amendola, A., Spada, M., Covaceuszach, S., et al. (2003). Anti-nerve growth factor Ab abrogates macrophage-mediated HIV-1 infection and depletion of CD4+ T lymphocytes in hu-SCID mice. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 100(15), 8927-8932 [10.1073/pnas.1332627100].

Anti-nerve growth factor Ab abrogates macrophage-mediated HIV-1 infection and depletion of CD4+ T lymphocytes in hu-SCID mice

GARACI, ENRICO;PERNO, CARLO FEDERICO;
2003-01-01

Abstract

Infection by HIV-1 causes persistent, long-term high virus production in macrophages. Major evidence, both in humans and in primate models, shows the crucial role of macrophages in sustaining virus production and in mediating a cytopathic effect on bystander CD4+ T lymphocytes and neuronal cells. In the present study, we used severe combined immunodeficient (SCID) mice engrafted with human peripheral blood lymphocytes (hu-PBL-SCID mice) to investigate the in vivo effect of HIV-1-infected macrophages on virus spread and CD4+ T lymphocyte depletion, and the ability of a mAb against nerve growth factor (NGF, a neurokine essential for the survival of HIV-1-infected macrophages) to suppress the pathogenetic events mediated by infected macrophages. Injection of mice with as few as 500 HIV-exposed macrophages causes (i) complete depletion of several millions of autologous CD4+ T lymphocytes, (ii) sustained HIV viremia, and (iii) spreading of HIV-1 DNA in mouse lymphoid organs. In contrast, in vivo treatment with an anti-NGF Ab completely abrogates all effects mediated by HIV-infected macrophages. Taken together, the results demonstrate the remarkable power of macrophages in sustaining in vivo HIV-1 infection, and that such a phenomenon can be specifically abrogated by an anti-NGF Ab. This may open new perspectives of experimental approaches aimed at selectively eliminating persistently infected macrophages from the bodies of HIV-infected patients.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/07 - Microbiologia e Microbiologia Clinica
English
Con Impact Factor ISI
nerve growth factor antibody; virus DNA; animal cell; animal experiment; animal model; article; controlled study; female; human; human cell; Human immunodeficiency virus 1; Human immunodeficiency virus infection; in vivo study; latent virus infection; lymphocyte depletion; macrophage; mouse; nonhuman; pathogenesis; persistent virus infection; priority journal; SCID mouse; T lymphocyte; viremia; virus replication; Animals; Antibodies, Monoclonal; CD4-Positive T-Lymphocytes; HIV Infections; HIV-1; Humans; Lymphocyte Transfusion; Lymphopenia; Macrophages; Mice; Mice, SCID; Nerve Growth Factor; Neutralization Tests; Transplantation, Heterologous; Viremia; Animalia; DNA viruses; Human immunodeficiency virus; Human immunodeficiency virus 1; Primates; RNA viruses
Garaci, E., Aquaro, S., Lapenta, C., Amendola, A., Spada, M., Covaceuszach, S., et al. (2003). Anti-nerve growth factor Ab abrogates macrophage-mediated HIV-1 infection and depletion of CD4+ T lymphocytes in hu-SCID mice. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 100(15), 8927-8932 [10.1073/pnas.1332627100].
Garaci, E; Aquaro, S; Lapenta, C; Amendola, A; Spada, M; Covaceuszach, S; Perno, Cf; Belardelli, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/52008
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