Scientists develop technique to decipher the dormant AIDS virus concealed in cells

September 11, 2012, Gladstone Institutes

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 , the laboratory of Gladstone Investigator Leor Weinberger, PhD, announced the development of a device that can pinpoint and track HIV inside —the type of white blood cell that the targets. This development is particularly important for understanding "HIV latency," a state in which the virus goes dormant after the patient begins standard . Current 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 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 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 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 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."

Explore further: Drug helps purge hidden HIV virus, study shows

Related Stories

Drug helps purge hidden HIV virus, study shows

March 8, 2012
A team of researchers at the University of North Carolina at Chapel Hill have successfully flushed latent HIV infection from hiding, with a drug used to treat certain types of lymphoma.

Vaccination strategy may hold key to ridding HIV infection from immune system

March 8, 2012
Using human immune system cells in the lab, AIDS experts at Johns Hopkins have figured out a way to kill off latent forms of HIV that hide in infected T cells long after antiretroviral therapy has successfully stalled viral ...

HIV havens: Researchers find new clues about how HIV reservoirs may form

August 17, 2011
Much like cities organize contingency plans and supplies for emergencies, chronic infectious diseases like HIV form reservoirs that ensure their survival in adverse conditions. But these reservoirs—small populations ...

Recommended for you

HIV-1 genetic diversity is higher in vaginal tract than in blood during early infection

January 18, 2018
A first-of-its-kind study has found that the genetic diversity of human immunodeficiency virus type 1 (HIV-1) is higher in the vaginal tract than in the blood stream during early infection. This finding, published in PLOS ...

War in Ukraine has escalated HIV spread in the country: study

January 15, 2018
Conflict in Ukraine has increased the risk of HIV outbreaks throughout the country as displaced HIV-infected people move from war-affected regions to areas with higher risk of transmission, according to analysis by scientists.

Researchers offer new model for uncovering true HIV mortality rates in Zambia

January 12, 2018
A new study that seeks to better ascertain HIV mortality rates in Zambia could provide a model for improved national and regional surveillance approaches, and ultimately, more effective HIV treatment strategies.

New drug capsule may allow weekly HIV treatment

January 9, 2018
Researchers at MIT and Brigham and Women's Hospital have developed a capsule that can deliver a week's worth of HIV drugs in a single dose. This advance could make it much easier for patients to adhere to the strict schedule ...

New long-acting, less-toxic HIV drug suppresses virus in humanized mice

January 8, 2018
A team of Yale researchers tested a new chemical compound that suppresses HIV, protects immune cells, and remains effective for weeks with a single dose. In animal experiments, the compound proved to be a promising new candidate ...

Usage remains low for pill that can prevent HIV infection

January 8, 2018
From gritty neighborhoods in New York and Los Angeles to clinics in Kenya and Brazil, health workers are trying to popularize a pill that has proven highly effective in preventing HIV but which—in their view—remains woefully ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.