Research The main topic of our research is the molecular basis of innate antiviral defenses. We investigate how distinctive molecular patterns associated with infection are recognized by the innate immune system, and what defense mechanisms block viral replication within cells. We are particularly interested in restriction factors—host proteins that disrupt specific steps in the viral life cycle and form the first line of defense against viruses. Evolutionary antagonism between viruses and their hosts’ rest
TRIM5α restriction factors bind retroviral capsids after cell entry and impair reverse transcription and nuclear import of the viral genetic material. Species-specific sequence variations within TRIM5α proteins contribute to host tropism of primate immunodeficiency viruses. Most notably, the human TRIM5α has poor affinity for the HIV capsid making humans susceptible to AIDS. We are interested in how primate TRIM5α proteins recognize retroviral capsids and how they impair viral infectivity. Our studies revea
SAMHD1 is an innate immune factor with roles in antiretroviral defenses and in interferon signaling. SAMHD1 catalyzes hydrolysis of deoxynucleotides (dNTPs) to triphosphate and unphosphorylated nucleosides and acts as a key regulator of dNTP supply in the cell. Retroviral restriction is thought to arise from the SAMHD1-catalyzed depletion of cellular dNTPs, which directly impairs the ability of the virus to complete reverse transcription of its genome. Controlled depletion of dNTPs is likely an ancient anti