Immunology, Transplantation and Infectious diseases

Immunobiology of HIV

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Group Leader

Lucia Lopalco

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This unit focuses on the structure-immunogenicity applied to the host-virus relationship and in particular we study alterations of self repertoire associated to reduced susceptibility to HIV infection or development of tumors. The analyses of the immune factors involved in immune controls could be extremely relevant to generate strategies able to prevent viral transmission. CCR5 cellular protein is the main coreceptors for HIV and natural antibodies (Abs) to CCR5 showed HIV-blocking properties, both in CD4+ T lymphocytes and in epithelial cells, thus interfering with mucosal HIV transmission. The mechanism of action of these Abs is different from that reported for other CCR5 specific molecules. Natural Abs to CCR5 specifically inhibit HIV replication by inducing a full and long lasting CCR5 downregulation with a very slow kinetic (48h). In an experimental BalB/c mouse model, full in vivo CCR5 downregulation, as well as receptor back-regulation, follow a very slow kinetics that was gradually recovered in 4 weeks after immunization. 

Research activity

Research activity is aimed at creating an immune barrier by targeting the host rather than the virus establishing a durable elimination of CCR5. The receptor internalization by anti-CCR5 Abs requires β-arrestin2, which may couple ligand-activated receptors to clathrin, and lead to a cytoplasmatic CCR5 accumulation with consequent activation of ERK1. Such signalosoma turn from Class A trafficking short term pattern, normally used for its internalization with natural modulating molecules (RANTES), into a long lasting Class B type specifically induced by stimulation with anti-CCR5 Abs. This new pathway is relevant not only to study in depth the molecular basis of all pathologies where CCR5 is involved but also to generate new antidody-based therapeutics and vaccines. The unit is also involved in the identification of hepatocarcinoma (HCC) specific mutated self-proteins and development of monoclonal antibodies against new HCC epitopes.