Researchers leading way in the fight against HIV

In the 1980s, when AIDS started ravaging communities around the world, many people reacted to the disease with panic.

With no cure and little information about the illness, there was a climate of fear similar to last year’s outbreak of Ebola in West Africa.

“There [were] a lot of people who felt they did not know about the epidemic and they were afraid,” James Bunn, one of the co-founders of World AIDS Day, told National Public Radio. “And they were right to be afraid because of the things that they were hearing.” Bunn said sick people “were being ostracized by their families. They were being evicted from their homes because they were sick and dying.”

Bunn, who worked back then as a public information officer at the World Health Organization in Geneva, teamed up with his colleague Thomas Netter and came up with the idea to celebrate the first World AIDS Day on Dec. 1, 1988.

Bunn told NPR that when they started, they focused on the story of a girl with AIDS who could go to school only if she was inside a glass enclosure. Today, governments and nonprofits spend billions on treatment, prevention and education, and people view AIDS (acquired immune deficiency syndrome) more like a chronic ailment than the lurking monster it once seemed.

One direct result of the push to demystify AIDS was the development of antiretroviral drugs. They keep the HIV virus that causes AIDS under control in the body and allow patients to live longer and more productive lives. The obvious next step is finding a cure.

Some 34 million people around the world live with HIV and AIDS, including 3.2 million children. HIV attacks immune cells called T-cells, replicating itself and infecting other cells. As AIDS develops, it leaves the body susceptible to infections and diseases it would otherwise easily fight off.

Thomas Hope, professor of cell and molecular biology at the Hope HIV Laboratory at Northwestern University, is taking a closer look — literally.

Dr. Hope is using a high-definition microscope developed by GE Healthcare Life Sciences to study how HIV particles infect a cell and then spread to other cells. His goal is to prevent the initial infection. This microscope — GE Healthcare Deltavision OMX™ — is so powerful that scientists call it the OMG microscope. The device uses advanced algorithms and high-definition cameras that allow researchers to observe living organisms and viruses in 3D even beyond Ernst Abbe’s diffraction barrier, once the final frontier for microscopic resolution. (The barrier prevented researchers from seeing two objects closer to each other than half the wavelength of light they used to image the sample.) As a result, scientists can use it to study objects as small as 120 nanometers, about 1,000th the width of a piece of human hair.

Unlike a typical microscope, the machine does not have an ocular lens or a traditional stand. Instead, scientists place samples on a platform inside the machine and photograph them using high-definition cameras. Rather than shining light at the sample, they attach colored fluorescent molecules, called probes, to parts of viruses and cells. The light emitted by the probes then illuminates things that were previously obscured.

The technology allows Dr. Hope and his team to highlight different segments of the HIV virus and the cells it tries to infect. “We’re really starting to identify which cells get infected first, and where they are located,” Dr. Hope says. “That sets the stage for us to really begin to pick that apart. The Deltavision became … the instrument of choice for a whole lot of HIV work.”

At Emory University, Paul Spearman is using the GE Healthcare Deltavision Core and the OMX microscopes, along with GE Healthcare Life Sciences’ AKTA™ Protein Purification Systems, to study how HIV assembles, replicates and gets released from infected cells.

One of the pathways his team has been dissecting is that which places the HIV envelope protein (Env) onto developing particles. By manipulating cellular recycling pathways, Spearman and his team have been able to arrest Env trafficking in a discrete compartment called the endosomal recycling compartment. By trapping Env in this compartment, the viruses that assemble are rendered noninfectious. “We have nice evidence of disrupting envelope trafficking and stopping the spread of the virus,” Spearman says. “We have been using Deltavision for about seven years, and now we are learning new details of the assembly pathway using the OMX.”

He says once the Env trafficking pathway is fully understood, he can work on developing an inhibitor.

The Deltavision system isn’t the only GE technology researchers are using to find a cure for HIV. Dr. James Crowe, director of the Vanderbilt Vaccine Center, uses GE Healthcare Life Sciences technology to isolate, purify and characterize batches of individual monoclonal antibodies in order to study people who are unusually resistant to HIV. He believes these patients — called “controllers” or “nonprogressors” — could hold the key to developing a vaccine.

Controllers live as long as 20 years before HIV becomes AIDS — twice as long as most patients. “We take blood cells from HIV-infected people, particularly those who are able to control their infections,” Crowe says. “There may be clues in their immune response as to how to resist HIV. We’re studying antibodies made by these individuals.”

He is getting closer to finding out what makes them special, and how to leverage their unique immune response to reach the holy grail of HIV research: a vaccine.

Working in a high-safety laboratory, he mixes the purified monoclonal antibodies with live HIV cells and incubates them. “Then we see if the virus can still replicate in cells, and if the antibodies inhibit the replication of the virus … a process called neutralization,” he says. “That’s the function we’re looking for. That’s the moment of truth: when we know if these antibodies are really potentially useful.”

Cindy Collins, general manager of in vitro diagnostics, research and applied markets at GE Healthcare Life Sciences, says, “A decade ago, it seemed unimaginable that we might one day see a cure for HIV. While much work remains to be done, the groundbreaking work of these researchers gives us hope that this may not be such a far-off reality. Our focus is to continue to develop the technology that will enable and advance their research.”

The GE Healthcare Deltavision OMX™ and AKTA™ Protein Purification Systems are for research use only. They are not for diagnostic or therapeutic purposes.