IDENTIFICAZIONE DI TRE NUOVI PEPTIDI SALIVARI BASICI RICCHI DI PROLINA CARATTERIZZATI DA ATTIVITÀ ANTI- HIV-1

Although important progress has been achieved in preventing new HIV infections and in lowering the annual number of AIDS-related deaths, the number of people living with HIV ineluctably increases. As well known, actual antiretroviral therapies are unfortunately characterized by very marked side effects and the drug resistance problem continues to be a daily issue; so the necessity to extend the list of the new anti-HIV drugs remain a constant priority. The existence of HIV latent reservoirs is one the major obstacle to eradicate the virus from human body hence to successfully treat the HIV infection. These reservoirs are extremely stable, so that it seems rather unrealistic to definitely succeed in the eradication of the virus by using the current therapeutic regimens. Consequently, the identification of new antiretroviral drugs, able to eradicate HIV from its reservoirs, has became a pressing priority. Unlike other mucosal area of the body, the oral cavity appears to be an extremely uncommon transmission route for HIV [13]. In addition to the distinct oral mucosal architecture and cellular constituents, oral fluids, unlike other mucosal secretions, are rarely a vehicle for HIV infection. One reason for this apparent paradox is the presence of endogenous mucosal antiviral factors, including neutralizing antibodies, secretory leukocyte protease inhibitor (SLPI), antiviral peptides such as defensins and cystatins, glycoproteins including thrombospondin and lactoferrin, and complement components [14]. In 2001 Robinovitch MR demonstrated the presence in human parotid saliva of specific basic proline-rich proteins possessing significant anti-HIV-1 activity independent of that attributable to SLPI or TSP-1. In this thesis are presented for the first time tree salivary proline-rich basic peptides showing the surprising and unexpected ability to inhibit HIV-1 in vitro replication without exerting cytotoxic effects on human PBMC. In addiction, these peptides demonstrate to be potent inducers of the viral replication in the ex vivo assays. This aspect, which would seem contradictory, represents a very innovative effect, considering the latent viral reservoirs problem. In conclusion, these peptides could target viral reservoirs and eradicate HIV from human body by firstly inducing the replication of latent virus in cells and then inhibiting it. Moreover, the peptides here analized even show antifungal activity, particularly useful to treat the opportunistic infections AIDS associated.