amfAR announces inaugural Mathilde Krim Fellowship Awards for AIDS research

HIV Tat-mediated transfer of P-TEFb to nascent RNA and its inhibition: In order to successfully reproduce, HIV must make full-length copies of its entire genome as well as copies of each of its genes. In order to ensure that full-length copies are made, the virus recruits a cell protein, P-TEFb, which interacts with a segment of the virus called Tat. Dr. D’Orso plans to elucidate the precise details of the process whereby Tat and P-TEFb bind together and the structure of these protein complexes. Understanding the process of assembly and the shape taken by these proteins when they are bound together will help point towards potential therapies aimed at disrupting the vital relationship between the two proteins.

Felipe Diaz-Griffero, Ph.D./Mentor: Joseph Sodroksi, M.D.
Dana-Farber Cancer Institute, Inc., Boston, MA
$125,000

Modulation of HIV-1 reverse transcription and integration by TRIM5: Successful infection requires that the virus undergo several transformations before inserting itself into the human DNA. Several proteins within human and animal cells can prevent HIV infection from occurring and are largely the reason most other animals cannot be infected with HIV. Dr. Diaz-Griffero plans to determine whether one such infection-blocking protein, TRIM5alpha from rhesus monkeys, can block the successful completion of HIV infection not only before but after the virus converts itself to DNA. Understanding the various ways in which HIV infection can be blocked may aid in the development of therapies that enhance these infection-blocking proteins in humans.

Kushol Gupta, Ph.D./Mentor: Gregory Van Duyne, Ph.D.
The University of Pennsylvania School of Medicine, Philadelphia, PA
$125,000

Biophysical and structural studies of the HIV integrase-DNA complex: In order for HIV infection to take place and to initiate reproduction, HIV must insert itself into the human DNA of the cell it has infected. The process whereby it finds its way to the nucleus of the cell and inserts itself into the DNA is incompletely understood, though researchers know that the HIV DNA must bind to the HIV enzyme integrase as well as the cell protein LEDGF. Dr. Gupta plans to use an array of technologies to generate the first atomic-level illustrations detailing the ways in which these three components bind together to accomplish the integration of HIV DNA into human DNA.

Nolwenn Jouvenet, Ph.D./Mentor: Paul Bieniasz, Ph.D.
Aaron Diamond AIDS Research Center, New York, NY
$125,000

Morphogenesis and storage of HIV-1 particles: As a final step in the process of reproduction, various components of newly made viruses gather inside the wall of the cell in which they are reproducing. From there, they are assembled into whole viruses that then either bud out of the cell or are absorbed into compartments inside the cell. It is suspected that these internal compartments that sequester the virus might contribute to the ability of the virus to persist in an infected person despite vigorous immune system and drug therapy attacks. Dr. Jouvenet will use sophisticated microscope technology to study the sequestration process and the circumstances under which the virus eventually buds out of the cell, ultimately boosting our understanding of the barriers to curing HIV infection.