Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: A possible protective effect against disease progression

Claudia Pastori, Barbara Weiser, Claudia Barassi, Caterina Uberti-Foppa, Silvia Ghezzi, Renato Longhi, Giliola Calori, Harold Burger, Kimdar Kemal, Guido Poli, Adriano Lazzarin, Lucia Lopalco

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4825-4833
Number of pages9
JournalBlood
Volume107
Issue number12
DOIs
StatePublished - Jun 15 2006
Externally publishedYes

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Disease Progression
Anti-Idiotypic Antibodies
HIV
Antibodies
HIV-1
Highly Active Antiretroviral Therapy
Virus Diseases
Epitopes
Down-Regulation
Vaccines
T-cells
Lymphocytes
Tissue Donors
T-Lymphocytes
Infection
Population
Therapeutics

ASJC Scopus subject areas

  • Hematology

Cite this

Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors : A possible protective effect against disease progression. / Pastori, Claudia; Weiser, Barbara; Barassi, Claudia; Uberti-Foppa, Caterina; Ghezzi, Silvia; Longhi, Renato; Calori, Giliola; Burger, Harold; Kemal, Kimdar; Poli, Guido; Lazzarin, Adriano; Lopalco, Lucia.

In: Blood, Vol. 107, No. 12, 15.06.2006, p. 4825-4833.

Research output: Contribution to journalArticle

Pastori, C, Weiser, B, Barassi, C, Uberti-Foppa, C, Ghezzi, S, Longhi, R, Calori, G, Burger, H, Kemal, K, Poli, G, Lazzarin, A & Lopalco, L 2006, 'Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: A possible protective effect against disease progression', Blood, vol. 107, no. 12, pp. 4825-4833. https://doi.org/10.1182/blood-2005-06-2463
Pastori, Claudia ; Weiser, Barbara ; Barassi, Claudia ; Uberti-Foppa, Caterina ; Ghezzi, Silvia ; Longhi, Renato ; Calori, Giliola ; Burger, Harold ; Kemal, Kimdar ; Poli, Guido ; Lazzarin, Adriano ; Lopalco, Lucia. / Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors : A possible protective effect against disease progression. In: Blood. 2006 ; Vol. 107, No. 12. pp. 4825-4833.
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