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.
Biology and evolution of retroviruses is closely tied to that of the cells that they parasitize. The consequences of retroviral infection are diverse, from lethal immunodeficiency to benign insertion into the host genome. The Bieniasz laboratory studies the molecular biology of retrovirus replication, with an emphasis on human and primate immunodeficiency viruses.
As well as determining the functions of viral genes and proteins, Dr. Bieniasz’s research seeks to define how the replication of retroviruses is influenced by host genes and pathways. Some host functions are manipulated or exploited by retroviruses to enable replication while others have evolved specifically to provide defenses against retrovirus infection.
How the virion components are generated and assembled into infectious particles is one focus of Dr. Bieniasz’s efforts. His earlier work, using biochemical genetic and imaging approaches, revealed many details of the virus particle assembly process, including the recruitment of host proteins that drive assembly and particle budding. Current interests include defining how viral RNA splicing stability, transport, translation, and packaging into virions is regulated.
Another major area of interest is intrinsic host defenses against retroviruses. Throughout their evolution, most eukaryotic organisms have frequently been colonized by retroviruses. Indeed, selection pressures imposed by ancient retroviral infections are likely responsible for shaping the array of host defense mechanisms that currently influence susceptibility to modern retroviruses such as HIV-1. The Bieniasz laboratory works on several types of intrinsic defenses to understand the mechanistic details by which they inhibit retrovirus replication. Two such inhibitors, discovered in the Bieniasz laboratory, include tetherin, which inhibits the release of a wide range of enveloped viruses from the surface of infected cells, and Mx2, which targets the capsid of HIV-1 to inhibit viral entry into the nucleus of target cells. New types of antiretroviral defenses and the mechanisms by which they work are currently being investigated.
Infection of germ line cells has left a fossil record of ancient retroviruses, and Dr. Bieniasz has pioneered the field of “paleovirology” by reconstituting functional versions of extinct retroviral proteins. Understanding how ancient retroviruses were extinguished may give clues about how to combat modern viral infections.
The Bieniasz laboratory is also working to derive more useful animal models of AIDS virus infection in monkeys and mice. Recently, his laboratory developed an HIV-1 strain that can cause AIDS in macaques. These new animal models should provide testing grounds for new forms of therapy and vaccination.
Dr. Bienasz is a faculty member in the David Rockefeller Graduate Program and the Tri-Institutional M.D.-Ph.D. Program.