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

49 Scopus citations

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

ASJC Scopus subject areas

  • Hematology

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    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, 107(12), 4825-4833. https://doi.org/10.1182/blood-2005-06-2463