Novel Capsid-Interacting Cellular Factors in HIV Uncoating

Cheryl Stoddart, University of California, San Francisco
Basic Biomedical Sciences
Innovative, Developmental, Exploratory Award (IDEA)

The absence of a vaccine and the limitations of current HIV therapeutic regimens have prompted the investigation into alternate methods to prevent or delay the progression of HIV disease. Because drugs that target the virus invariably lose their potency because HIV develops resistance, targeting cellular proteins required for virus replication is an increasingly attractive avenue for intervention. HIV is an obligate parasite and is dependent on the host cell for virtually every step of the virus life cycle. However, we have a limited working knowledge of the numerous cellular proteins essential for HIV replication. We previously reported on a mutant strain of HIV that had impaired replication capacity but that could overcome this defect when exposed to cells that were activated through an external stimulus. These findings suggested the existence of host cell proteins in activated cells that could rescue the mutant virus, and we pursued this hypothesis to identify six cellular factors that not only rescue the mutant virus but that are also essential for replication of wild-type HIV. Here, we propose experiments aimed at determining more precisely the relationship between the newly identified host factors and HIV replication. More importantly, identification of novel HIV-interacting cellular factors may provide additional targets for much needed, novel therapeutic interventions.