beneficial effect of trail on hiv burden, without detectable immune consequences有益的线索对艾滋病毒负担的影响,没有检测到免疫的后果.pdfVIP

Beneficial Effect of TRAIL on HIV Burden, without Detectable Immune Consequences 1 2 1 3 1 Brett D. Shepard , Davide De Forni , David R. McNamara , Andrea Foli , Stacey A. Rizza , 1 1 1 4 1 Roshini S. Abraham , Keith Knutson , Peter J. Wettstein , Franco Lori , Andrew D. Badley * 1 Mayo Clinic, Rochester, Minnesota, United States of America, 2 Virostatics s. r. l., Sassari, Italy, 3 Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy, 4 Research Institute for Genetic and Human Therapy, Pavia, Italy Abstract Background: During uncontrolled HIV disease, both TNF-related apoptosis inducing ligand (TRAIL) and TRAIL receptor expression are increased. Enhanced TRAIL sensitivity is due to TRAIL receptor up-regulation induced by gp120. As a result of successful antiretroviral therapy TRAIL is down-regulated, and there are fewer TRAIL-sensitive cells. In this setting, we hypothesized that all cells that contain virus, including those productively- and latently-infected, have necessarily been ‘‘primed’’ by gp120 and remain TRAIL-sensitive, whereas uninfected cells remain relatively TRAIL-resistant. Methods and Findings: We evaluated the immunologic and antiviral effects of TRAIL in peripheral blood lymphocytes collected from HIV-infected patients with suppressed viral replication. The peripheral blood lymphocytes were treated with recombinant TRAIL or an equivalent amount of bovine serum albumin as a negative control. Treated cells