A new study by the collaboration of European Molecular Biology Laboratory and Heidelberg University Hospital revealed a detailed analysis of an immature form of HIV cells and how a new HIV drug prevents the virus from maturing.
The study, published in the journal Science, showed that a newly developed HIV drug could prevent the maturity of HIV cells by locking them in place.
"When we looked at the virus with one of these inhibitor drugs on it, we found that the inhibitor doesn't prevent the cutting machinery from getting in, as you might expect," explained Florian Schur, who carried out the work in John Briggs' lab at EMBL, in a statement. "Rather, the drug locks the immature virus structure in place, so that it can't be cut."
The immature form of HIV is assembled inside an infected cell. For this cell to mature, it needed to cut the connections between its main building blocks, known as the capsid protein and the spacer peptide 1, and rearrange those pieces. If the building blocks were not cut, the virus cannot mature.
However, HIV with certain mutations developed resistant against the new drug making them unaffected. In order to understand the effects of those mutations, the researchers used a combination of cryo-electron tomography and subtomogram averaging to reveal exactly what this part of the immature form of HIV looks like in 3D.
The researchers found out that the virus became resistant to the new drug not by preventing or blocking its effects, but by circumventing them.
"Rather than stopping the drug from binding, the virus becomes resistant through mutations that destabilise the immature structure," the researchers noted in a press release. "This allows it to rearrange and be cut even when the drug is in place."
With the use of the combined cryo-electron tomography and subtomogram averaging, the researchers can study the structures of irregular virus like HIV in their real state. This method of observing the state of the virus and how certain drugs affects their structure can be used in the future development of new drugs to cure the dreaded disease.