Researchers at the Salk Institute have uncovered the 3D structures of HIV integrase during two distinct roles in the virus's replication cycle, revealing its structural flexibility and how it adopts different conformations for each function.

This structural plasticity allows integrase to switch between a large, multi-part form for DNA integration and a smaller form for interacting with viral RNA, which is crucial for the virus's replication process.

Understanding these conformational changes opens new avenues for drug development, particularly targeting integrase's RNA interaction to combat drug resistance and improve HIV treatments.

The study, published in Nature Communications on October 24, 2025, utilized cryo-electron microscopy to capture detailed images of integrase in its different functional states.

This groundbreaking research was supported by multiple NIH grants, private foundations, and institutions, emphasizing its importance for future HIV therapeutic strategies.

The findings provide critical insights into the enzyme's dual functions—facilitating viral DNA integration and interacting with viral RNA—by revealing how structural changes enable these roles.