Anti-nerve growth factor Ab abrogates macrophage-mediated HIV-1 infection and depletion of CD4+ T lymphocytes in hu-SCID mice.
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
Enrico
E
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy.
Aquaro
Stefano
S
Lapenta
Caterina
C
Amendola
Alessandra
A
Spada
Massimo
M
Covaceuszach
Sonia
S
Perno
Carlo-Federico
CF
Belardelli
Filippo
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1; D006801:Humans; D017710:Lymphocyte Transfusion; D008231:Lymphopenia / Q000517:prevention & control; D008264:Macrophages / Q000276:immunology / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000276:immunology; D009500:Neutralization Tests; D014183:Transplantation, Heterologous; D014766:Viremia / Q000209:etiology / Q000276:immunology / Q000517:prevention & control
D000911:Antibodies, Monoclonal; D020932:Nerve Growth Factor