Identification of a new therapeutic target and a potential therapeutic candidate for the treatment of HIV infection

A comparative proteomics analysis conducted in MT4 cells showed that the expression levels of vimentin were downmodulated after treatment with a fraction of the dialyzable leukocyte extract which shows anti-HIV-1 activity. The relationship of this intermediate filaments (IF) forming protein with the viral replication cycle was then elucidated by establishing a knockdown cell line expressing low levels of vimentin. The early stages of HIV-1 replication were safely evaluated in this cell line, by using a third-generation lentiviral vector which expressed the green fluorescent protein. Using this challenge system as well as the replicative HIV infection assay, it was evidenced for the first time that a reduction in vimentin expression levels drastically affects HIV-1 replication. It was demonstrated by transmission electron microscopy and fluorescence microscopy techniques that a synthetic peptide derived from the keratin-10 protein (denominated CIGB-210) modifies vimentin IFs, also showing a potent inhibitory activity and remarkably low cell toxicity. This makes of CIGB-210 a promising therapeutic candidate against HIV/AIDS. Altogether, our results showed that vimentin is involved in the early stages of viral infection and could be a potential target for the development of novel drugs against HIV/ AIDS. This work was granted with the Annual Award of the National Academy of Sciences of Cuba for the year 2016.