HIV

Juan Cubillos-Ruiz at Weill Cornell Medical College in the U.S. will develop silica nanopore-based assays to capture unique low molecular weight proteins and identify biomarkers associated with host resistance to HIV. Identifying these biomarkers present in the small proportion of HIV-infected individuals who are able to suppress the virus over the long term could lead to new understanding of the processes mediating HIV resistance and to new therapies against the disease.

Janet Hapgood of the University of Cape Town in South Africa will use ex vivo primary epithelial cell models and cervical tissue explants to investigate how different progestins currently used in contraceptives might affect susceptibility to and transmission of HIV-1.

Daniel Nixon and colleagues at Virginia Commonwealth University in the U.S. will test the theory that gut bacterial flora (microbiome) and nutrition influence inflammation, immune activation, and HIV disease progression. The team will determine whether a safe, inexpensive probiotic bacteria oral supplement can treat an abnormal gut microbiome and attenuate immune system deterioration in HIV-infected Malian women.

Shengxi Chen of Arizona State University in the U.S. will design and prepare a fluorescent sCD4 protein that changes color when it binds to the HIV pg120 protein. By directly detecting a virus protein instead of antibodies or RNA, which take days to months to accumulate sufficiently to detect, HIV infection can be diagnosed immediately to help prevent the spread of the epidemic.

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.