Ann Arbor Times

University of Michigan researchers have provided new insights into the mechanisms by which HIV exploits cellular transportation systems. Their study challenges a long-standing theory and introduces a method for examining viral components outside of cellular environments, potentially aiding in identifying new drug targets.

The internal workings of cells involve constant movement, with motor proteins acting like delivery vehicles along microtubules. HIV utilizes this system to navigate within host cells, attaching itself to dynein motor proteins to reach the nucleus and integrate its genetic material into the host genome.

Since the early 2000s, it was believed that HIV required a cargo adaptor protein, specifically BicD2, to connect with dynein. However, research from U-M Life Sciences Institute now indicates that HIV can directly attach to dynein without BicD2. The study found that any dynein adaptor protein could initiate movement, offering the virus flexibility in its mode of transport.

“This reconstitution system allows us to view just the pieces we want to investigate,” said Michael Cianfrocco, associate professor at U-M Medical School and LSI. Using purified components on microscope slides, researchers observed how HIV interacts with dynein directly.

The study reveals that different adaptor proteins present in various cells expand HIV's options for reaching cell nuclei. "This opens a new perspective on how infection is happening," noted Somaye Badieyan from Cianfrocco’s lab.

This research marks a pioneering example of viral trafficking using reconstituted components and presents opportunities for further investigation into viral infections. “This study introduces a new way to think about direct viral attachment,” said Cianfrocco.

The research received support from the National Institutes of Health and involved collaborators from Loyola University Chicago, University of New South Wales, Australia; and Vanderbilt University Medical Center.