Heads of Laboratories
Paul Bieniasz, Ph.D.
Investigator, Howard Hughes Medical Institute
Aaron Diamond AIDS Research Center
Laboratory of Retrovirology
The biology and evolution of retroviruses and eukaryotes are closely linked. Dr. Bieniasz seeks to define how host gene products influence the replication of retroviruses, with an emphasis on human and primate immunodeficiency viruses. There are two dominant research areas in his lab: characterizing the host-cell factors and pathways that are mimicked, manipulated and otherwise exploited by retroviruses, and studying host functions that have evolved specifically to defend cells against retrovirus infection.
One major focus of Dr. Bieniasz’s lab is determining how retrovirus structural proteins are transported, assembled and released from cells as infectious particles. The role of host factors and pathways in these processes has been one of the most enigmatic areas in retrovirology, but one that is gradually becoming clearer. For example, Dr. Bieniasz has shown that many enveloped viruses — retroviruses included — specifically recruit components of a cellular pathway that normally mediates the budding of vesicles into the lumen of endosomes. Dr. Bieniasz found that viral proteins redirect vesicle budding and ubiquitin ligation machinery to sites of virus assembly in order to facilitate the formation of an enveloped virus particle. Other related problems that the lab is investigating include defining how retroviral proteins select the locations within the cell at which they’re assembled; in particular, how they are affected by the cellular environment and host molecules as well as the intrinsic membrane binding and multimerizing properties of retroviral Gag proteins.
A second major area of interest is “intrinsic immunity.” Evolution has equipped mammals with several gene products specifically to prevent or attenuate retrovirus replication. Intrinsic immunity differs from classical innate immunity in that it doesn’t seem to require any form of signaling or intercellular communication to be activated. Rather, it apparently consists of constitutively expressed intracellular proteins that exhibit potent antiretroviral activity. Dr. Bieniasz works on three classes of inhibitors. One class (exemplified by Fv1 and TRIM5) blocks infection by targeting incoming retrovirus capsids. Prior research by Dr. Bieniasz has shown that this class of inhibitors prevents HIV-1 infection in cells from some nonhuman primates. The human version of this inhibitor protects against some retroviruses, but not HIV. A second class is comprised of cytidine deaminases (such as APOBEC3G) that induce lethal hypermutation of retroviral genomes.
Recently, research from the Bieniasz lab has identified a third type of antiviral molecule, called tetherin, that prevents virus particles from being released from the cell surface and moving off to infect other cells. Dr. Bieniasz has also found that HIV uses another protein, called Vpu, to counteract tetherin and allow budding virus particles to depart from the cell surface.
Understanding how these cellular antiretroviral activities work and how some retroviruses, particularly primate immunodeficiency viruses, have acquired new functions that confer resistance to them could provide new opportunities to develop novel therapies and improved animal models of AIDS. To that end, the Bieniasz lab recently developed a strain of HIV-1 that can infect pig-tailed macaques. The virus differs from that found in humans by a single gene that protects it from the monkey’s APOBEC3 inhibitors. With further work, the new strain, dubbed simian tropic HIV-1, could provide a reliable animal model for testing HIV vaccines and other treatments.
Dr. Bieniasz received his undergraduate degree in biochemistry from the University of Bath in 1990 and his Ph.D. in virology from Imperial College, University of London, in 1996. He was a postdoc at Duke University until 1999, studying molecular retrovirology, and then accepted positions as a staff investigator at the Aaron Diamond AIDS Research Center (ADARC) and as an assistant professor at Rockefeller. In 2003 he was named by ADARC an Aaron Diamond Associate Professor at The Rockefeller University and in 2004 was promoted by Rockefeller to associate professor, head of laboratory.
Dr. Bieniasz was a 2003 recipient of the Elizabeth Glaser Scientist Award from the Elizabeth Glaser Pediatric AIDS Foundation and the 2010 recipient of the Eli Lilly and Company Research Award. He is also an investigator at the Howard Hughes Medical Institute.
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