Nav: Home

Mount Sinai researchers track HIV in real time as it infects and spreads in living tissue

June 09, 2016

By watching brightly glowing HIV-infected immune cells move within mice, researchers at the Icahn School of Medicine at Mount Sinai have shown how infected immune cells latch onto an uninfected sister cell to directly transmit newly minted viral particles. These interactions allow HIV to spread efficiently between these immune cells, known as CD4+ helper T cells. The research, published online today in Cell Reports, challenges the long-held perception that the primary route of HIV infection of immune cells is from free-floating viral particles that move within tissue and blood fluids.

While HIV cell-to-cell transmission has been observed in test tube experiments, this is the first study to capture these interactions in a living animal. Although cell-to-cell infection does result in release of abundant solo viral particles, direct transmission from HIV-infected immune cells to other cells -- which can then replicate in clusters of these cells -- is a much more efficient route to quickly spread the virus, researchers say. It may be particularly important in allowing the virus to spread in the body even before it is detectable in the blood.

Previous studies in cell culture have indicated that cell-to-cell infection may help HIV to resist antibodies and potent therapies. This study provides direct evidence that these interactions do occur in infected immune tissues, and highlight the importance of considering cell-to-cell transmission in developing new treatments.

"All HIV treatment to date has been based on the free-floating virion model," says Benjamin K. Chen, MD, PhD, an Associate Professor of Infectious Diseases, Microbiology, and Immunology at the Icahn School of Medicine at Mount Sinai. "We believe that the sensitivity to antibodies used as potential HIV treatment and to certain antiretroviral drugs can be decreased by cell-to-cell transmission. Agents that efficiently block cell-to-cell transmission may help reduce the HIV viral reservoir, and vaccines that can neutralize this transmission may also help prevent or control HIV."

HIV, or human immunodeficiency virus, is a virus that attacks the body's immune system. If left untreated, HIV can progress and develop into AIDS (acquired immunodeficiency syndrome). More than 1.2 million people in the United States are living with HIV infection. Globally, more than 39 million people have been infected.

Glowing proteins track HIV movement

Lead author Kenneth M. Law, a graduate fellow in Dr. Chen's laboratory, attached green fluorescent molecules derived from jellyfish and red glowing proteins from coral onto variants of HIV. The researchers then introduced the two strains into mice transplanted with a human immune system and watched in real time as HIV spread from one CD4+ helper T cell to another.

"We could visualize hot spots of infection within lymphoid tissue, which has millions of cells moving dynamically within the tissue," says Mr. Law. "By focusing just on the green and red glowing cells, we could monitor how an infected cell influences uninfected cells."

Using an advanced imaging technique called intravital microscopy, the researchers followed the movement and interaction of HIV-infected cells in the spleen of mice. They watched as infected cells induced contact with uninfected cells, and the uninfected cell would then pause for a time on the infected cell--building a physical connection between them.

Scientists describe these infectious connections as virological "synapses" because they resemble the way that cells of the nervous system or the immune system communicate through intimate cell-to-cell connections.

A mutation factory

The investigators believe the proteins that make up the HIV virion are being assembled at the site of the bridge and then directly moved to the cell being infected. Cell-to-cell infection allows several viruses to simultaneously pass between the connected cells. The researchers found that multiple viruses could infect a single cell through virological synapses.

This pathway allows multiple copies of HIV to transmit together from cell to cell, a genetic property that can help mutant viruses to accumulate. This may help explain the high mutation rate that allows the virus to escape from immune responses, says Mr. Law. "The genetic mixing that happens when a cell is infected with multiple HIV virions can lead to novel genetic recombination that then gets passed into the next immune cell that is infected."
-end-
Co-authors of the study include Alice W. Yewdall, Rebecca K. Lee and Olga L. Herrera, from the Icahn School of Medicine at Mount Sinai; and Dominik Wodarz and Natalia L. Komarova from the University of California, Irvine.

The study was supported by the National Institute on Drug Abuse (F31DA036425, R01AI074420, R01AI093998, and Avant Garde DA028866), the National Institute of General Medical Sciences (GM113885), and Burroughs Wellcome Investigators in the Pathogenesis of Infectious Disease Fund.

About the Mount Sinai Health System

The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services -- from community-based facilities to tertiary and quaternary care.

The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is ranked as one of the nation's top 10 hospitals in Geriatrics, Cardiology/Heart Surgery, and Gastroenterology, and is in the top 25 in five other specialties in the 2015-2016 "Best Hospitals" issue of U.S. News & World Report. Mount Sinai's Kravis Children's Hospital also is ranked in seven out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology, while Mount Sinai Beth Israel is ranked regionally.

For more information, visit http://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.>

The Mount Sinai Hospital / Mount Sinai School of Medicine

Related Immune System Articles:

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.
Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.
COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.
Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.
Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.
Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.
Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.
How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.
Immune system upgrade
Theoretically, our immune system could detect and kill cancer cells.
Using the immune system as a defence against cancer
Research published today in the British Journal of Cancer has found that a naturally occurring molecule and a component of the immune system that can successfully target and kill cancer cells, can also encourage immunity against cancer resurgence.
More Immune System News and Immune System Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.