Imagine that HIV is a sealed tin can: if you opened it, what would you find inside? An international team led by researchers at the University of Montreal Hospital Research Centre (CRCHUM), Tufts University School of Medicine, and the University of Melbourne think they know. For the first time, they have visualized what the “open can” of the human immunodeficiency virus looks like, revealing a previously unknown virus shape and a very detailed image of the vulnerabilities of the virus.
Published April 10 in the journal Cell Host & Microbe, this major breakthrough was made possible through the use of a molecular “can opener” to expose parts of the virus envelope that can be targeted by antibodies.
“The characterization of the new shape of the virus envelope reveals unique details about the vulnerability of HIV that might be useful in strategies aimed at its eradication,” said Andrés Finzi, one of the lead authors of the study, a researcher at the CRCHUM and a professor at University of Montreal. “It certainly opens new paths in the fight against this deadly virus.”
When HIV infects cells of the human immune system, it uses its envelope’s spike to attach itself to specific receptors on the cells, called CD4 and CCR5. Binding to the CD4 receptor triggers changes in the shape of the envelope that allow the virus to infect the host cell. The new research describes the use of small-molecule CD4-mimetic compounds designed and synthesized at the University of Pennsylvania to force the virus to open up and to expose vulnerable parts of its envelope, allowing the immune system cells to kill the infected cells.