Novel Method Tracks HIV Life Cycle

Findings may lead to new targeted treatment options for HIV infection.

For the first time, scientists from Northwestern Medicine successfully identified individual particles associated with HIV-infection using a novel fluorescent imaging system, according to a report by News Medical Life Sciences.

It is known that HIV fuses to a target immune cell during infection to deliver its capsid onto the cytoplasm. Using the process uncoating, the capsid disassembles to hijack the cell’s function.

Despite this, the specific mechanisms of uncoating have been debated, with some believing the process occurs late at pores and others suggesting the uncoating takes place earlier and in the cytoplasm, News Medical reported.

In a study published in the Proceedings of the National Academy of Sciences, investigators sought to distinguish between viral particles that lead to cell infection and those that do not.

The investigators developed a novel live-cell fluorescent imaging system to identify individual particles linked with infection, according to News Medical.

Using this method, the investigators monitored how the HIV capsid uncoats in the cell at the individual particle level, revealing that the uncoating occurred in the cytoplasm approximately 30 minutes after cell fusion.

“Being able to connect infectivity of individual particles and how they behave in the cell to infection—–which is what we really care about––is going to have a big impact on the field,” principal investigator Thomas Hope told News Medical. “The system can now be used to resolve other controversies in HIV biology and to determine which potential targets for drug development are most relevant.”

These findings may lead to the development of new HIV treatment options and prevention, the authors noted.

“This approach—–and the ability to say, ‘that virion infected that cell’––will help bring clarity to the field,” Hope told News Medical. “It allows us to understand what the virus really needs to do to infect a cell. It gives us new details, like where in cell it happens and the timing of specific events. The more we know about the virus, the better our chances are to stop it.”

First author João Mamede mentioned the technique could be applied to more than just HIV, “theoretically, you could apply this technique to the study of any fluorescently-tagged virus.”

The authors plan to utilize the novel method in future studies to examine infection in later stages of the HIV lifecycle, according to News Medical.

“We want to understand all the details, from when the virus fuses, to the point where it integrates and starts to make new viruses, to the last phase,” Hope told News Medical. “We need to understand what’s going on, so we can find the Achilles’ heel of the virus and use it as a drug target.”