Our laboratory is interested in the replication of mammalian retroviruses, including the human immunodeficiency virus (HIV) and Moloney murine leukemia virus (M-MuLV). The major approach has been to alter cloned DNA copies of the viral genome by site-directed mutagenesis, and to determine the effects of these mutations on the viral life cycle after transfer of the altered DNAs into cells in culture. These genetic analyses have defined the functional domains of various viral proteins and the sites of their action on viral nucleic acids. We have also expressed reverse transcriptase and integrase in bacteria and studied these enzymes biochemically. We have applied the yeast two-hybrid system to monitor protein-protein interactions between viral proteins, and to identify new host proteins that interact with the Gag, Pol and Env gene products. We are also screening overexpression cDNA libraries, and RNAi knock-down libraries, in mammalian cells to identify novel host proteins involved in retroviral infection.

HHMI