HIV

Alberto Bosque of the University of Utah in the U.S. will use high-throughput transcriptome analysis to identify and characterize unique biomarkers expressed on latent HIV infected memory cells in an effort to design new therapeutic strategies to eradicate HIV infection.

Eugenio Montini of Fondazione Centro San Raffaele Del Monte Tabor in Italy will attempt to identify the specific cellular genes that HIV uses to integrate into cells and establish latency. Discovering these "common insertion sites" could lead to therapies for preventing HIV latency.

Zhengxian Gu and colleagues at PTC Therapeutics, Inc. in the U.S. will investigate the mechanism of action used by a class of small molecules shown to specifically activate HIV. Understanding the pathways for reactivation of latent HIV could inform development of drug therapies to eliminate latent HIV reservoirs and effectively cure HIV.

Seth Pincus of Children's Hospital New Orleans in the U.S., armed with knowledge that CD4+ memory cells that express the biomarker CD45RO harbor latent HIV, will test how depleting CD4+ memory cells harboring latent HIV can affect the latent HIV reservoir and the immune system in general.

Terri Finkel of The Children's Hospital of Philadelphia in the U.S. will test whether synthetic BET (bromodomains and extraterminal) protein antagonists can inhibit the replication of HIV and the establishment of latency, while also promoting the reactivation of latently infected cells. Such molecules could be used to control and cure HIV infection.

Phillip M. Gerk of Virginia Commonwealth University in the U.S. will test the ability of fatty acid transporters to deliver antiretroviral drugs to the central nervous system and gut-associated lymphatic tissues, which provide sanctuary for latent HIV.

Thor Wagner of Seattle Children's Hospital in the U.S. will use high-throughput single-cell screening of activated B-cells from HIV patients on antiretroviral therapy in an effort to identify antibodies that bind specifically to HIV-infected cells. These antibodies could be used to develop antibody drug conjugates to kill HIV-infected cells.

Adrienne Wilk of the University of Illinois at Chicago in the U.S. will investigate whether post-translational modification of S-acylated cell surface proteins alters the plasma membrane of cells with latent HIV infection. If so, these S-acylated proteins could be used to identify such latently infected cells that cannot be detected using current diagnostic methods.

Marco Sgarbanti at the Istituto Superiore di Sanità in Italy proposes to develop a new class of small molecules designed to mimic Tat gene products found in HIV that stimulate and accelerate the transcription of HIV RNA. These Tat-mimicking compounds could activate the latent virus, creating an opportunity to expose it to effective antiretroviral therapies.

Russell Poulter of the University of Otago in New Zealand will test 'homing' endonucleases found in the genomes of some microbes for their ability to precisely cleave DNA at very specific sites. If successful, these nucleases could be suitable for cleaving and eliminating integrated HIV.