Right now, 34 million people around the world are living with HIV and AIDS, including 3.2 million children.
Ever since the virus began to reach epidemic levels in the 1980s, scientists have been racing to find a cure. While many patients now benefit from forms of ART (Anti-Retroviral Therapy) that prolong life expectancy and can help patients lead relatively ‘normal’ lives, there is no outright cure or vaccine.
However, Dr. Thomas J Hope, Professor of Cell and Molecular Biology and leader of the Hope HIV Laboratory at Northwestern University, believes a cure or effective prevention approach could be on the horizon.
He has pioneered several new approaches to studying HIV. Using advanced methods, some of which he developed himself, Dr. Hope is able to directly observe individual HIV particles in action, from the moment they infect a cell to the moment they are transmitted to other cells.
Using GE Healthcare Life Sciences’ Deltavision OMXTM*, a high-definition microscope that has been dubbed ‘the OMG microscope’, Dr. Hope uses fluorescence to highlight different parts of the HIV virus and the cells it tries to infect. In addition to giving us beautiful images, this method is the key to observing different processes as they happen in cells.
What is HIV?
HIV (Human Immunodeficiency Virus) is a virus that only infects humans, and it is one that our immune systems cannot destroy on their own. The virus’ main target is the cells of our immune system, called T-cells.
The virus attacks these cells and uses them to make copies of itself, which then break out and infect other nearby cells. This seriously weakens the immune system, and once a certain number of T-cells are destroyed, AIDS (Acquired Immune Deficiency Syndrome) develops, and the body is left susceptible to infections and diseases it would normally fight off with ease.
For instance, a common infection seen in AIDS patients is Toxoplasmosis. This is a serious disease caused by a parasite that reproduces in cats. Up to a third of us have it, but our immune system keeps it in check. It is one of the first infections AIDS patients can succumb to once their T-cell count falls below a certain level.
Biological pathways, intracellular mechanisms, and chemical processes that were once hidden from view have nowhere to hide now that Dr. Hope can see them from every angle. By observing every step of HIV’s life cycle, he is discovering exactly how the virus works, biologically, chemically and mechanically. And once you learn how something works, you can learn how to break it.
“Using these visualization techniques, we actually discovered that HIV [particles] move along inside the cell on microtubules,” said Dr. Hope. “Otherwise the viral genome would have to try to get to the cell nucleus through random motions. That’s just one of the things we discovered early on.”
As described in GE Reports, the Deltavision OMXTM* uses powerful algorithms to process the images the microscope takes and breaks through the diffraction barrier. For a long time, the barrier prevented researchers from seeing two objects closer to each other than half the wavelength of light they used to image the sample. But by attaching colored fluorescent molecules, called probes, to different parts of the virus or cells, the light shines from the sample.
“We were among the first who pushed that, and ultimately the Deltavision became the instrument of choice for a whole lot of HIV work.”
The cameras in the Deltavision OMXTM* are incredibly high-definition, but the real key is the deconvolution part. Essentially, this is the computer-based reconstruction of the image that allows Dr. Hope to take out-of-focus light and put it back where it originated, by calculating how light scatters along a certain path under the microscope.
This kind of image restructuring may be more familiar than you think, as it is the same used to piece together the Hubble Telescope’s stunning images of space.
“The technology has come a long way since the late 90s,” added Dr. Hope. “We have a number of different ways that we can label the viral particles.”
“We can look at up to about five different [fluorescent] colors simultaneously. If you try to do that in living cells, it gets significantly more complex and challenging to add colors [to different cell components].”
This allows Hope’s team to label the virus in such a way that they can see where an HIV particle’s membrane fuses with a cell’s membrane. Then they can see the components that get dumped into the cell and where they go from there on their life cycle of replication and transmission through the body.
“I started off looking at how individual [HIV particles] move within cells,” he said. “Then we began looking at multiple cells interacting and how the virus plays a role there… and now we’re actually trying to understand the transmission of the virus by looking at tissues and tissue sections in pretty great detail.”
Armed with this knowledge, Dr. Hope can ask the right questions about HIV. He is currently looking at ways of preventing the first few infected cells from getting infected at all in the first place.
“I think we’re really starting to identify which cells get infected first, and where they’re located. And that sets the stage for us to really begin to pick that apart.”
Leading up to World AIDS Day on December 1, The Pulse is taking a close look at the pioneering work of three leading scientists, pushing the boundaries of science to find a cure. Stay tuned to learn about how Dr. Crowe is harnessing the power of people who can naturally ‘control’ their HIV, and how Dr. Spearman is working to find the weak spot that will stop HIV dead in its tracks.
*The Deltavision OMXTM is for research use only. It is not for diagnostic or therapeutic purposes.