Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: a possible protective effect against disease progression.
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.
Pastori
Claudia
C
Infectious Diseases Clinic, San Raffaele Scientific Institute, 20127 Milan, Italy.
Weiser
Barbara
B
Barassi
Claudia
C
Uberti-Foppa
Caterina
C
Ghezzi
Silvia
S
Longhi
Renato
R
Calori
Giliola
G
Burger
Harold
H
Kemal
Kimdar
K
Poli
Guido
G
Lazzarin
Adriano
A
Lopalco
Lucia
L
D016915:AIDS Vaccines / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018450:Disease Progression; D015536:Down-Regulation / Q000276:immunology; D004705:Endocytosis / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006679:HIV Seropositivity / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007152:Immunologic Capping / Q000276:immunology; D008297:Male; D017434:Protein Structure, Tertiary; D019713:Receptors, CCR5 / Q000097:blood / Q000276:immunology*
D016915:AIDS Vaccines; D001323:Autoantibodies; D000939:Epitopes; D019713:Receptors, CCR5