Structural studies of viral replication and invasion

Abstract
Viruses are a major threat to human health. Our laboratory uses various structural biology techniques to
dissect molecular mechanisms of how viruses replicate and invade the host cell or its genome. One area of our
major interest is retroviral integration, a critical step in the lifecycle of retroviruses that achieves permanent
insertion of the reverse-transcribed viral genome into a host chromosome. We will build on our recent structural
studies of the Human T-cell Leukemia virus and Rous sarcoma virus intasomes and further investigate the
roles of host factors during integration of these retroviruses. Another area that we are pursuing is the
replication of coronavirus RNA genomes and host cell invasion. In particular, we are interested in how a virally
encoded exoribonuclease complex facilitates faithful replication of the large RNA genomes of coronaviruses,
and how this unique proofreading activity could be modulated by small molecules. We are also investigating
inhibition of the receptor binding of the coronavirus spike protein by novel antibodies and antibody-mimics.
Overall, the studies proposed in this application will help better understand important RNA-based human
pathogens and could aid in the development of antiviral strategies, or alternatively, gene delivery tools useful in
research or gene therapy applications.

Grant Number: 5R35GM118047-09
NIH Institute/Center: NIH
Principal Investigator: Hideki Aihara