February 2009: Cutting-Edge amfAR Grants Fight HIV/AIDS in the Lab and on the Phone

$1.6 million awarded in new round of HIV/AIDS research grants and fellowships

Contact: Jennifer Samuels, Coordinator, Program Communications, (212) 806-1756, jennifer.samuels@amfar.org 

FOR IMMEDIATE RELEASE
NEW YORK, February 19, 2009—Most parents of teenage children have experienced frustration at their sons’ and daughters’ obsession with text messaging. But what if this ubiquitous technology could be used to save lives? At the University of Dar es Salaam in the East African nation of Tanzania, a country where few have landlines but most own a cell phone, that is precisely what Dr. Joyce Nyoni is trying to do.

amfAR, The Foundation for AIDS Research, today announced that it will fund three projects, including the work of Dr. Nyoni, that are harnessing social networkingtechnologies to prevent the spread of HIV infection. Dr. Nyoni will recruit a small number of men who have sex with men (MSM), who in turn will recruit other MSM, to receive and send regular text messages containing HIV/AIDS information. At the end of her study, Dr. Nyoni will assess the changes in knowledge and behavior that she hopes will result from the program. In addition to searching for novel ways to prevent HIV infection, at the other end of the research spectrum amfAR announced the award of six new grants for innovative biomedical research studies aimed at advancing the treatment and cure of HIV/AIDS.

On the 200th anniversary of Charles Darwin’s birth, it is fitting perhaps that one of the grantees will use our deepening understanding of evolution to identify new targets for anti-HIV drugs.  Dr. Sara Sawyer of the University of Texas at Austin will base her study on the Red Queen hypothesis, which suggests that organisms must continue to evolve just to keep up with the other organisms that surround them. Arguing that mutations in cell proteins that compromise HIV’s ability to grow will be favored over time, Dr. Sawyer hopes to identify those that show the greatest promise as drug targets.

A third group of awards is allocated specifically to younger scientists who often have the greatest difficulty finding support for their work but who represent the long-term viability of AIDS research.  Four of these Mathilde Krim Biomedical Research Fellowships were awarded for a total of close to $500,000. Only in its second year, the Krim Fellowships have already yielded spectacular results. In January alone, three Krim Fellows authored papers in leading scientific journals describing novel strategies for vaccine development, drug design, and prevention of heterosexual transmission of HIV. The new Fellowship recipients will examine viral latency and new targets for microbicide and anti-HIV drug development.

 “HIV does not slow down in a recession,” said Dr. Rowena Johnston, amfAR’s vice president and director of research. “In fact it’s more important than ever to fund projects with the potential to help those who are hit hardest in times like these. These new awards focus on the fundamental needs of the field of HIV/AIDS research: new prevention technologies, new treatments, recruitment of young researchers, and progress towards a cure.”

The projects being funded are:

Krim Fellowships

Alberto Bosque, Ph.D./Mentor: Vicente Planelles, Ph.D.
University of Utah, Salt Lake City, UT$125,000
Studies of HIV-1 latency and reactivation using a novel ex-vivo model: A small number of long-lived cells persistently infected with latent virus are thought to be the main barrier to a cure for HIV infection. Testing new therapeutic strategies requires laboratory tools that faithfully replicate the conditions of this viral latency and persistence. Dr. Bosque and colleagues have developed just such a model consisting of primary cells in which virus has integrated in a normal manner. Using his newly developed model, Dr. Bosque plans to explore the sequence of events inside infected cells that help to establish this viral latency, the signals that reactivate the virus, and potential therapeutics that can affect the establishment of latency and virus reactivation.

Jan de Rijck, Ph.D./Mentor: Zeger Debyser, M.D., Ph.D.
Katholieke Universiteit Leuven, Leuven, Belgium
$125,000
Characterization of transportin-SR2 mediated nuclear import of HIV: Studies in the past year have identified hundreds of proteins in host cells that play mostly as yet unidentified roles in assisting HIV throughout its lifecycle within infected cells. Dr. de Rijck plans to elucidate the role of one such protein, transportin-SR2 (TRN-SR2), in conveying the virus into the nucleus so that it can integrate into the DNA. He is particularly interested in identifying those regions of TRN-SR2 that interact with the HIV protein integrase.  His additional studies to create defective versions of TRN-SR2 will test the suitability of this protein interaction as a new target for drug development.

Fedde Groot, Ph.D./Mentor: Quentin Sattentau, Ph.D.
University of Oxford, Oxford, United Kingdom
$124,782
Macrophage-T cell interactions in formation of the HIV-1 reservoir: Immune cells, the targets of HIV infection, communicate among themselves conveying information concerning infections and how best to counteract them. When such communication occurs by physical contact between cells, HIV can subvert this process by moving from an infected cell (effector) to an uninfected cell (target) at the point of contact, and thus HIV can spread rapidly in the body. Dr. Groot will examine the role played by cell-to-cell spread of HIV in the establishment of latent viral reservoirs, the identity of effector and target cells, and how the response of the immune system may affect the extent to which the reservoir can be established.

Navid Madani, Ph.D./Mentor: Joseph Sodroski, M.D.
Dana-Farber Cancer Institute, Boston, MA
$125,000
A chemical campaign to identify HIV-1 entry inhibitors: Microbicides have been envisioned as a means of preventing the sexual transmission of HIV, but to date human trials of such products have not been successful. Preventing the earliest events in virus transmission constitutes an ideal point of intervention, thus Dr. Madani is interested in identifying chemicals that inhibit the entry of HIV into susceptible cells. She will take advantage of three new technologies and a detailed understanding of structural elements of the envelope protein on the virus to identify new compounds, and to improve upon known compounds, that can block viral entry. Such compounds would represent ideal active ingredients in new microbicide products.

Social and behavioral –  Applying social networking technologies to the prevention of HIV infection

Hongjie Liu, Ph.D.
Virginia Commonwealth University, Richmond, VA
$119,930
A pilot study of a text-messaging-enhanced POL HIV intervention program: Men involved in transactional sex with other men represent an important source of HIV transmission in China, especially since condom usage rates are low. Dr. Liu will design and test an education and prevention intervention in which male sex workers receive information both face-to-face as well as via text messaging from popular opinion leaders (POLs). These are people who are both popular and influential within the male sex worker community. POLs will be trained to provide appropriate information, and male sex workers will be surveyed both before and after the intervention to measure changes in behaviors such as condom use.

Willi McFarland, M.D.
STOP AIDS Project, San Francisco, CA
$102, 421
Assessing internet users’ preference for structural and network interventions: The rise in the use of the internet by men to find male sex partners appears to be associated with an increased risk of acquiring HIV, but most websites do not provide tools men can use to select partners in ways that minimize their chances of becoming infected. Dr. McFarland and his colleagues plan to query internet users, website owners, and public health officials from around the country to identify those interventions that are most likely to effectively reduce HIV risk. The findings from this study will help website owners design and select content that will be of most benefit to their clients’ health.

Joyce Nyoni, Ph.D./Mentor: Joe Lugalla, Ph.D.
University of Dar es Salaam, Dar es Salaam, Tanzania
$114,109
Cell phone use among MSM in stigmatized settings: implications for HIV: In many regions of the world, including Tanzania, sex between men is highly stigmatized. As a result, reaching members of communities who are at very high risk of acquiring HIV with appropriate education and support is very difficult. Dr. Nyoni plans to recruit a small number of men who have sex with men (MSM), who will in turn recruit more MSM to take part in this project in which they will receive regular text messages on their cell phones containing HIV/AIDS information. Men will also have the opportunity to ask questions via SMS. Changes in knowledge and behavior as a result of this program will be evaluated.

Biomedical – Exploring novel antiretroviral targets and inhibitors

Devin Christensen, Ph.D./Mentor: Wesley Sundquist, Ph.D.
University of Utah, Salt Lake City, UT
$125,000
Identifying cellular cofactors of Rhesus monkey TRIM5-alpha: While the evolutionary struggle between viruses and primates has yielded several proteins that can prevent disease caused by HIV, the virus is armed with its own proteins to counteract these defenses. Slight differences in the protein TRIM5-alpha between rhesus monkeys and humans mean that the rhesus form of the protein can inhibit HIV infection while the human form cannot. Dr. Christensen will document which cell proteins cooperate with rhesus TRIM5-alpha to overcome HIV. Understanding these additional cooperative functions may serve as the basis of new therapeutics that either mimic or enhance the blockade of the virus that occurs in monkeys.

Dana Gabuzda, M.D.
Dana-Farber Cancer Institute, Inc., Boston, MA
$120,000
High-throughput screens for inhibitors of Vif-APOBEC3G interaction: Over the past few years, scientists have discovered several proteins that have developed over evolutionary history that can counteract viruses including HIV. The first of these to be discovered, APOBEC3G, is extraordinarily potent in destroying HIV, and so the virus has responded with a defense of its own, a viral protein called Vif, that can prevent APOBEC3G from degrading HIV within infected cells. Dr. Gabuzda plans to search through approximately one hundred thousand compounds at Harvard University for small molecules that can inhibit the interaction between Vif and APOBEC3G and that might ultimately serve as the basis for a new drug to reinstate the ability of APOBEC3G to degrade HIV.

Jing Jin, Ph.D./Mentor: Walther Mothes, Ph.D.
Yale University School of Medicine, New Haven, CT
$125, 000
Cellular factors required for HIV cell-to-cell transmission: A cell can become newly infected with HIV either by contact with a cell-free virus, or with a virus inside an infected cell. Cell-to-cell transmission of HIV is vastly more efficient, and therefore Dr. Jin seeks to understand which cell proteins cooperate in the transmission of a virus from an infected cell to an uninfected one. She will also identify small molecules with the potential to inhibit those proteins that enhance the transmission of HIV between cells. These small molecules could serve as the basis for the development of therapeutics to slow the spread of infection inside the body.

Akira Ono, Ph.D.
The University of Michigan, Ann Arbor, MI
$120,000
The role of PIP2 as a cofactor for HIV-1 assembly at the plasma membrane: After co-opting many cell proteins and processes in manufacturing its various parts, HIV assembles itself close to the membrane of the cell it has infected. Dr. Ono plans to elucidate which cell proteins help ensure that constituent parts of the virus come together in an appropriate fashion. He is particularly interested in a cell lipid called PIP2 that binds to the viral protein Gag, a core protein that defines the physical structure of the virus. If, as he suspects, PIP2 is critical for the assembly of HIV, researchers may be able to devise therapeutics that could disrupt the formation of new viruses.

Lee Ratner, M.D., Ph.D.
Washington University School of Medicine, St. Louis, MO
$120,000
Target of Vpr/Vpx restriction: HIV makes proteins that are important both to its physical structure and others that regulate the way in which the virus interacts with the host cells it infects.  One of the least studied of the latter group, Vpr, and its close relative Vpx (which is found in the less common form of HIV known as HIV-2) are believed to promote HIV growth by enabling the virus to overcome some of the obstacles involved in infecting inactive cells. Dr. Ratner plans to characterize cell proteins whose function may be affected by Vpr and Vpx, thus permitting infection.

Sara Sawyer, Ph.D.
University of Texas at Austin, Austin, TX
$120,000
An evolutionary approach to identifying robust antiretroviral drug targets: The Red Queen hypothesis in evolutionary biology predicts that organisms must continue to evolve just to maintain their position in their environmental niche. Dr. Sawyer will use this principle to cull hundreds of proteins (co-factors) that have been identified as being important for promoting the HIV life cycle down to a useful group for further study. She argues that mutations in cell proteins that decrease the ability of retroviruses like HIV to grow will be favored over time. She will study the evolutionary history of these HIV cofactors to determine which appear to play the most important role and hence show great promise as targets for anti-HIV drug development.