Breakthrough Research Uncovers New Structural Role for HIV Protein Integrase
Research conducted by Professor Juan R. Perilla and his team at the University of Delaware, in collaboration with scientists in the U.S. and the United Kingdom, has revealed a previously unknown structural role for the HIV viral protein integrase.
Integrase, known for assisting HIV in inserting itself into human DNA, has now been shown to play a critical structural role during the virus's maturation into an infectious form. This significant finding was published on February 18 in Nature.
Integrase: More Than Just Insertion
Using high-resolution cryo-electron microscopy (cryo-EM), the research team observed a groundbreaking detail: integrase proteins form filaments that line the inside of the HIV capsid, the virus's protective shell.
These filaments are crucial, as they anchor the virus's RNA genome to the capsid's hexagon-shaped tiles. This intricate arrangement effectively organizes and packs the virus, preparing it for cellular infection.
Perilla stated that without these filaments, the virus is non-infective.
Advanced Techniques Illuminate Viral Structure
The comprehensive research involved sophisticated microscopy performed at the Francis Crick Institute, offering unprecedented views of the virus. Molecular modeling was utilized to detail atomic-level interactions, providing a deeper understanding of the processes involved. Furthermore, experimental studies employing inhibitors (ALLINIs) were conducted to disrupt integrase formation and its interactions with the capsid, confirming its structural importance.
New Hope for HIV Drug Development
This discovery identifies a crucial new target for drug development, as no existing FDA-approved drugs specifically target this structural role of integrase. The project received vital support from public funding agencies, including the U.S. National Science Foundation, National Institutes of Health, and U.S. Department of Energy, underscoring the collaborative effort across multiple institutions that made this breakthrough possible.