Scientists at the Gladstone Institutes have gotten us one step closer to understanding and overcoming one of the least-understood mechanisms of HIV infection—by devising a method to precisely track the life cycle of individual cells infected with HIV, the virus that causes AIDS.
In a paper being published online today in Lab on a Chip, the laboratory of Gladstone Investigator Leor Weinberger, PhD, announced the development of a device that can pinpoint and track HIV inside CD4 T cells—the type of white blood cell that the AIDS virus targets. This development is particularly important for understanding "HIV latency," a state in which the virus goes dormant after the patient begins standard antiretroviral treatment. Current antiretroviral drugs do not kill HIV—they only keep it at bay—meaning that those with HIV must continue a lifetime of drug treatment so as not to develop AIDS. If they discontinue the drugs, the latent virus "wakes up" within just a few weeks and begins an onslaught against the body's immune system.
The breakthrough comes as the AIDS-researcher community is beginning to speak publicly about the possibility of curing HIV/AIDS. Understanding—and consequently interrupting—HIV latency is a key element in the effort to discover a cure for this devastating disease.
"HIV latency is perhaps the single greatest obstacle to eradicating HIV/AIDS in the 34 million people who live with the disease worldwide," said Dr. Weinberger, who is also an associate professor of biochemistry and biophysics at the University of California, San Francisco (UCSF), with which Gladstone is affiliated. "Existing techniques that try to uncover the cellular and viral mechanisms behind HIV latency are inefficient at studying very rare cells—and cells housing the latent HIV virus are one-in-a-million. Our technique presents a clear path towards understanding how HIV latency is regulated within a single cell, by tracking the individual cells that traditionally had been difficult to monitor."
Singe-cell, time-lapse microscopy—a state-of-the-art technique that scientists have lately used to track some viral infections and map antibiotic resistance to drugs—has not worked for tracking the HIV-infection cycle in CD4 T cells, especially in the latent state. This is because these cells are notoriously evasive. They spontaneously move around, attaching and detaching from their neighbors, making it nearly impossible to monitor individual HIV-infected cells over time.
However, Dr. Weinberger's team devised a clever system that essentially guides and suspends HIV-infected T cells into tiny finger-like channels—reducing their ability to move or detach from their neighbors.
"First, we load the T cells into a small well, allowing them to settle into the bottom—which is filled with nutrients that keep the cells well-fed and stress-free," explained the paper's lead author Brandon Razooky, a Gladstone and UCSF graduate student. "Next, we tilt the device and the cells slide into microscopic finger-like channels that are attached to the well. Finally, we return the device to its upright position, locking about 25 T cells inside each channel and essentially 'freezing' them in place."
The device has several advantages over current methods. First and foremost, individual cells stay in place so investigators can follow them over time with single-cell, time-lapse microscopy. Second, the fact that each T cell is suspended in nutrients in close physical contact with other cells results in near optimal conditions for keeping the infected cell alive for the virus' entire life cycle.
"This means that we now have the potential to analyze the entire course of an HIV infection in an individual cell—especially during the crucial latency stage—for which we know so little," said Dr. Weinberger. "In the future, we plan to expand the device's design to include a larger number of wells and channels to track HIV infection on a larger scale. We want to use the information gleaned here to finally unravel the mechanisms behind HIV latency. With that knowledge, we hope to devise a treatment to bring the latent virus out of hiding in order to flush it from a patient's system, once and for all."
This research was funded by the National Institutes of Health and the National Science Foundation.
About the Gladstone Institutes
Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Gladstone is affiliated with the University of California, San Francisco.
Anne Holden | EurekAlert!
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy