Tackling HIV: Genetic vs. Immune CCR5 targeting

Lopalco, Lucia

doi:10.4172/2155-6113.1000344

J AIDS Clin Res

2014

DOI: 10.4172/2155-6113.1000344

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Tackling HIV: Genetic vs. Immune CCR5 targeting

Lucia Lopalco¹

Abstract: Recent advances in gene targeting have proposed new approaches to treat HIV infection, focused on CCR5, which is a key molecule in virus entry as well as in infection maintenance. Ex vivo cell targeting could make T-cells resistant to infection while reducing cell reservoirs where HIV can escape total eradication. Immunization could provide prompt receptor down regulation and preventive immunity also in limited resources settings. Innovative, gene-based methods and immune-based interventions aimed at silencing… Show more

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The Role of Natural Antibodies to CC Chemokine Receptor 5 in HIV Infection

2017

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The CC chemokine receptor 5 (CCR5) is responsible for immune and inflammatory responses by mediation of chemotactic activity in leukocytes, although it is expressed on different cell types. It has been shown to act as co-receptor for the human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIV). Natural reactive antibodies (Abs) recognizing first loop (ECL1) of CCR5 have been detected in several pools of immunoglobulins from healthy donors and from several cohorts of either HIV-exposed but uninfected subjects (ESN) or HIV-infected individuals who control disease progression (LTNP) as well. The reason of development of anti-CCR5 Abs in the absence of autoimmune disease is still unknown; however, the presence of these Abs specific for CCR5 or for other immune receptors and mediators probably is related to homeostasis maintenance. The majority of anti-CCR5 Abs is directed to HIV binding site (N-terminus and ECL2) of the receptor. Conversely, it is well known that ECL1 of CCR5 does not bind HIV; thus, the anti-CCR5 Abs directed to ECL1 elicit a long-lasting internalization of CCR5 but not interfere with HIV binding directly; these Abs block HIV infection in either epithelial cells or CD4+ T lymphocytes and the mechanism differs from those ones described for all other CCR5-specific ligands. The Ab-mediated CCR5 internalization allows the formation of a stable signalosome by interaction of CCR5, β-arrestin2 and ERK1 proteins. The signalosome degradation and the subsequent de novo proteins synthesis determine the CCR5 reappearance on the cell membrane with a very long-lasting kinetics (8 days). The use of monoclonal Abs to CCR5 with particular characteristics and mode of action may represent a novel mode to fight viral infection in either vaccinal or therapeutic strategies.

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The Role of Natural Antibodies to CC Chemokine Receptor 5 in HIV Infection

2017

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Tackling HIV: Genetic vs. Immune CCR5 targeting

Cited by 1 publication

References 107 publications

The Role of Natural Antibodies to CC Chemokine Receptor 5 in HIV Infection

The Role of Natural Antibodies to CC Chemokine Receptor 5 in HIV Infection

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