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202 The MHC Class II Transactivator CIITA, a Restriction Factor for Human Retroviruses and a Molecule Making the Bridge Between Adaptive and Intrinsic Immunity

Accolla, Roberto S

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 86
doi: 10.1097/01.qai.0000397384.54438.2d

Department of Experimental Medicine, School of Medicine, University of Insubria, via Ottorino Rossi n.9, 21100 Varese, ITALY

Host defence against pathogens takes advantage of three mechanisms that co-evolved to ensure the best protection for the host: innate immunity, first barrier against pathogens; adaptive immunity, mediated by cells with specific receptor-mediated recognition and memory, and a third type of immunity, “intrinsic immunity” consisting in intracellular mechanisms that restrict pathogen infectivity and, in the case of certain viruses, intracellular pathogen replication. A number of viral retriction factors, are know, such as APOBEC and TRIM family members. These factors are functionally unrelated to molecules of the innate and adaptive immunity. Here I describe a viral restriction factor, the MHC class II transactivator CIITA, exerting its anti-replicative function on human retroviruses, including HIV, HTLV-1 and HTLV-2, and on the same time being one of the major regulator of adaptive immunity via its function on antigen presentation. Interestingly, although CIITA affects human retrovirus replication by inhibiting the function of the viral transactivators Tat, Tax-1 and Tax-2 of HIV-1, HTLV-1 and HTLV-2, respectively, its intimate molecular mechanism is different for the three viral transactivators. These characteristics make CIITA a unique example of viral restriction factor and a unique example of molecule bridging directly adaptive and intrinsic immunity during evolution.

Support: I.S.S. A.I.D.S. Project n° 45G.1.; Fondazione Cariplo 2008-2230; AIRC, grant IG 8862; MIUR Cofin 2008; FoCoVa 2009.

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