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New Approach Can Resolve Controversies in the Realm of HIV

AUG 31, 2017 | KRISTI ROSA
Many recent studies have contributed to the wealth of knowledge regarding HIV, such as research on the risks proton pump inhibitors present to patients with HIV, that older adults are being overlooked when it comes to prevention and treatment of the virus, and how home-based HIV testing kits may increase the number of at-risk individuals getting tested.

A new study coming in from Northwestern Medicine, however, delves deeper into the lifecycle of the virus. In fact, Northwestern Medicine researchers have developed a novel approach to track the virus by connecting the behavior of individual particles, known as virions, with infectivity, according to a recent press release.

Visualization of the behavior of these individual virons and their movement and behavior within cells has become somewhat routine; however, because many virions are either defective or do not go on to replicate, the relevance of this information was “previously unclear.”
When the virus infects a cell, it does the following:
  1. First, it will attach itself to a target immune cell.
  2. Then, it delivers its capsid, a cone that possesses the virus’s genetic material, to the cytoplasm of the cell.
  3. Next, the capsid will undergo a process called “uncoating,” which is essential to the infection process.
Views on the specific details of the “uncoating” process have been a bit controversial, with two schools of thought offering ideas. One camp believes that the process takes place later in the HIV lifecycle, at the pores, which allows “factors to enter the nucleus,” whereas the other camp suggests that “uncoating” actually occurs early on in the lifecycle of the virus, within the cytoplasm. The Northwestern researchers sought to determine which camp was correct.

In the study, the scientists utilized a live-cell fluorescent imaging system to provide these answers. For the first time, with the help of this system, the scientists were able to identify individual particles associated with infection, something previous methods have not been successful in accomplishing.

The scientists took a closer look at the uncoating process to learn more about the lifecycle of the virus. With the help of the imaging system, they were able to visualize the uncoating process “at the individual particle level.” As a result, they determined that the uncoating process occurs early on—about 30 minutes after the virus fuses to the cell—within the cytoplasm.

The scientists postulate that this imaging system can offer even more insights into the virus, and aid in the development of more approaches to fight against it.

Study author Thomas Hope, PhD, professor of cell and molecular biology, explained in the press release how the new approach offers new insights about the virus. “This approach—the ability to say, ‘that virion infected that cell’—will help bring clarity to the field,” he said. “It allows us to understand what the virus really needs to do to infect a cell. It gives us new details, like where in the cell it happens and the timing of specific events. The more we know about the virus, the better our chances are to stop it.”

He continued, “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. 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.”

João Mamede, PhD, a post-doctoral fellow in Dr. Hope’s laboratory, goes so far as to suggest that this imaging system could “theoretically” be used to study “any fluorescently-tagged virus,” which might be a game changer when it comes to virology research. For future research, the team wants to use the system to assess the infection during the later stages of the HIV lifecycle.

“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,” Dr. Hope shared. “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.”
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