Therapeutics/Drugs

Alison Hill and Daniel Scholes Rosenbloom of Harvard University in the U.S., working with Seyed Alireza Rabi and Greg Laird of Johns Hopkins University in the U.S., propose to engineer a gene therapy that delivers a viral transcription factor to reactivate CD4 cells that are latently infected with HIV along with a suicide gene that is triggered by HIV protein production to effectively kill the infected cells. This therapy could allow complete clearance of HIV from the body and a permanent cure for HIV infection.

R. Paul Johnson of Emory University in the U.S. is using single-cell transcriptional profiling to identify unique biomarkers expressed in CD4+ T cells latently infected with HIV or the simian equivalent SIV. Latent infection of long-lived cells enables the viruses to survive current drug treatments, and makes the disease very difficult to cure. In Phase I, while working at Harvard Medical School in the U.S., they developed a robust high-throughput technique to identify viral genes expressed in single cells and tested it on SIV-infected macaques.

Andres Finzi of the Centre Hospitalier de l'Université de Montréal in Canada will develop a system called "reverse fusion" in which viral-like particles that incorporate the HIV receptor CD4 and its co-receptors CCR5 and CXCR4 fuse specifically with HIV-infected cells to deliver toxic genes that kill the HIV-infected cells.

Mario Ostrowski of the University of Toronto in Canada will test the theory that alterations of host cells by HIV might also activate human endogenous retroviruses in the same cells. Ostrowski will express antigens of an endogenous retrovirus to study whether they might also mark HIV infected cells, providing a basis for the development of a new HIV vaccine.

Kathryn Miller-Jensen of Yale University in the U.S. will test the hypothesis that latently infected HIV cells produce different protein phosphorylation signatures than uninfected cells in response to drug treatments. Identifying these latent HIV cells will enable the design of new therapies that selectively target and purge these latent reservoirs.

Russell Poulter of the University of Otago in New Zealand will use a microbial biosynthesis platform to develop cyclic analogues of the viral protein Tat, which is major regulator of HIV transcription, and test their ability to activate latent HIV. The reactivated HIV would be susceptible to retroviral therapies enabling comprehensive killing of HIV infected cells.

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.