Michael Summers

Insights into the Mechanism of HIV Genome Packaging and Virus Assembly

The human immunodeficiency virus type 1 (HIV-1), the causative agent for AIDS, has caused nearly 30 million deaths over the past 30 years. An additional ∼33 million people are currently living with HIV-1 infection world wide, and in Washington D.C., one out of twenty adults is HIV positive. Combination drug therapies can keep the virus at bay for extended periods, even a normal lifespan, but current therapeutic regimes are expensive, compliance can be difficult, and strains that are resistant to combination drug therapies have emerged. Thus, there are needs to develop new therapeutic approaches that target different viral components.  The Summers lab is using nuclear magnetic resonance (NMR) to study the structures and functions of the viral proteins and RNA genome of HIV-1. They have determined the three dimensional structures of all of the major structural proteins of the virus, and have used this information to develop new methods for inhibiting virus replication in cultured human cells. Their most recent work has focused on developing new NMR tools that enable structural studies of large portions of the viral RNA that are required for genome packaging during virus assembly. Although the average size of RNAs that have been structurally characterized by NMR is 27 nucleotides, their new approach is providing structural information for the intact, dimeric 5´-Untranslated Region (5´-UTR) of the viral genome, which comprises 688 nucleotides. Their studies are yielding information on how the highly conserved viral 5´-UTR temporally regulates transcription, splicing, translation, packaging, reverse transcription, and other essential RNA-dependent activities during the viral replication cycle.