TY - JOUR
T1 - Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors
T2 - A possible protective effect against disease progression
AU - Pastori, Claudia
AU - Weiser, Barbara
AU - Barassi, Claudia
AU - Uberti-Foppa, Caterina
AU - Ghezzi, Silvia
AU - Longhi, Renato
AU - Calori, Giliola
AU - Burger, Harold
AU - Kemal, Kimdar
AU - Poli, Guido
AU - Lazzarin, Adriano
AU - Lopalco, Lucia
PY - 2006/6/15
Y1 - 2006/6/15
N2 - Exposure to HIV-1 does not necessarily result in infection and progression toward disease, thus suggesting that the control of viral infection may be achieved. Antibodies to CCR5 have been detected in HIV-exposed but uninfected subjects (ESNs); thus, these antibodies could be involved in HIV protection. To assess whether anti-CCR5 antibodies may also contribute to slow HIV disease progression, we searched for anti-CCR5 antibodies in 497 subjects, including 85 long-term nonprogressors (LTNPs), 70 progressors, 135 HIV+ patients treated with highly active antiretroviral therapy (HAART), and 207 seronegative donors. We found anti-CCR5 antibodies in a fraction of the LTNPs (23.5%) but not in the other populations studied (P < .001). These antibodies recognized a conformational epitope within the first extramembrane loop of CCR5, and they induced a stable and long-lasting downregulation of CCR5 on the surface of T lymphocytes, which inhibited HIV entry. In addition, CD4+ lymphocytes from LTNPs having anti CCR5 antibodies are resistance to R5 strains of HIV-1. Follow-up studies showed that the loss of anti-CCR5 antibodies occurred in some subjects, and this loss was significantly associated with a progression toward disease, whereas subjects who retained anti-CCR5 Abs maintained their LTNP status. Induction of anti-CCR5 Abs could be relevant to vaccine design and therapeutics.
AB - Exposure to HIV-1 does not necessarily result in infection and progression toward disease, thus suggesting that the control of viral infection may be achieved. Antibodies to CCR5 have been detected in HIV-exposed but uninfected subjects (ESNs); thus, these antibodies could be involved in HIV protection. To assess whether anti-CCR5 antibodies may also contribute to slow HIV disease progression, we searched for anti-CCR5 antibodies in 497 subjects, including 85 long-term nonprogressors (LTNPs), 70 progressors, 135 HIV+ patients treated with highly active antiretroviral therapy (HAART), and 207 seronegative donors. We found anti-CCR5 antibodies in a fraction of the LTNPs (23.5%) but not in the other populations studied (P < .001). These antibodies recognized a conformational epitope within the first extramembrane loop of CCR5, and they induced a stable and long-lasting downregulation of CCR5 on the surface of T lymphocytes, which inhibited HIV entry. In addition, CD4+ lymphocytes from LTNPs having anti CCR5 antibodies are resistance to R5 strains of HIV-1. Follow-up studies showed that the loss of anti-CCR5 antibodies occurred in some subjects, and this loss was significantly associated with a progression toward disease, whereas subjects who retained anti-CCR5 Abs maintained their LTNP status. Induction of anti-CCR5 Abs could be relevant to vaccine design and therapeutics.
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U2 - 10.1182/blood-2005-06-2463
DO - 10.1182/blood-2005-06-2463
M3 - Article
C2 - 16522810
AN - SCOPUS:33745077706
VL - 107
SP - 4825
EP - 4833
JO - Blood
JF - Blood
SN - 0006-4971
IS - 12
ER -