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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4825-4833. Prepublished online as a Blood First Edition Paper on March 7, 2006; DOI 10.1182/blood-2005-06-2463. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-06-2463v1 107/12/4825    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pastori, C. Articles by Lopalco, L. Search for Related Content PubMed PubMed Citation Articles by Pastori, C. Articles by Lopalco, L. Related Collections Immunobiology Chemokines, Cytokines, and Interleukins Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY 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, and Lucia Lopalco From the Immunobiology of HIV Unit, Infectious Diseases Clinic, San Raffaele Scientific Institute, Milan, Italy; theAIDS Immunopathogenesis Unit, Dibit, San Raffaele Scientific Institute, Milan, Italy; the Wadsworth Center, NY State Department of Health, Albany, NY; the Istituto di Biocatalisi e Riconoscimento Molecolare, Milan, Italy; the Clinic Research Office, San Raffaele Scientific Institute, Milan, Italy; the Università Vita-Salute San Raffaele, Milan, Italy; and the Laboratory for AIDS Vaccine Research and Development, Duke University Medical Center, Durham, NC. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Misumi, M. Masuyama, N. Takamune, D. Nakayama, R. Mitsumata, H. Matsumoto, N. Urata, Y. Takahashi, A. Muneoka, T. Sukamoto, et al. Targeted Delivery of Immunogen to Primate M Cells with Tetragalloyl Lysine Dendrimer J. Immunol., May 15, 2009; 182(10): 6061 - 6070. [Abstract] [Full Text] [PDF] C. Pastori, A. Clivio, L. Diomede, R. Consonni, G. M. S. De Mori, R. Longhi, G. Colombo, and L. Lopalco Two Amino Acid Substitutions within the First External Loop of CCR5 Induce Human Immunodeficiency Virus-Blocking Antibodies in Mice and Chickens J. Virol., April 15, 2008; 82(8): 4125 - 4134. [Abstract] [Full Text] [PDF] J. Catusse, C. M. Parry, D. R. Dewin, and U. A. Gompels Inhibition of HIV-1 infection by viral chemokine U83A via high-affinity CCR5 interactions that block human chemokine-induced leukocyte chemotaxis and receptor internalization Blood, May 1, 2007; 109(9): 3633 - 3639. [Abstract] [Full Text] [PDF] R. Soares, R. Foxall, A. Albuquerque, C. Cortesao, M. Garcia, R. M. M. Victorino, and A. E. Sousa Increased Frequency of Circulating CCR5+ CD4+ T Cells in Human Immunodeficiency Virus Type 2 Infection J. Virol., December 15, 2006; 80(24): 12425 - 12429. [Abstract] [Full Text] [PDF]

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