Journal News

How a virus can affect memory: The role of HIV in HAND

Nicole Lynn
Dec. 22, 2020

Human immunodeficiency virus destroys the white blood cells of the immune system, inhibiting the body's ability to fight infection. The stages of HIV range from acute to chronic; left untreated, HIV can progress to AIDS, which can be fatal.

JBC-HIV-infected-T-cell-445x334.jpg
Seth Pincus, Elizabeth Fischer and Austin Athman/National Institute
of Allergy and Infectious Diseases/NIH
Helper T-cells are important in directing the immune response against HIV.
In the image shown, a helper T-cell (shown in blue) is under attack by HIV
(shown in yellow), the virus known to cause AIDS.

A frequent outcome of HIV infection is HIV-associated neurocognitive disorders, or HAND. These disorders include a spectrum of mental and physical decline that affects behavior, memory and motor functions. While the development of antiretroviral therapy, or ART, has helped reduce the progression and severity of HAND, these disorders persist in 30% to 50% of infected individuals.

The mechanisms by which HIV infection promotes neurodegeneration are largely a mystery. However, ongoing collaborative research bridging the fields of virology and lipid and cell biology have brought researchers one step closer to an answer. In a recent study published in the Journal of Biological Chemistry, Dmitri Sviridov of the Baker Heart and Diabetes Institute together with Michael Bukrinsky of George Washington University investigated the relationship between Nef, an accessory protein secreted by cells infected by HIV-1, and the onset of HAND.

Nef is released from cells as cargo within extracellular vesicles (EVs); EVs are lipid bilayer particles unencumbered by the cell membrane. Even with administration of ART, the cells of HIV-infected individuals continue to secrete EVs containing Nef called ExNef. "A discovery that Nef is secreted in EVs from infected cells even during full suppression of virus production provided an important detail to our concept," Sviridov said.

JBC-schematic-445x278.jpg
Sviridov Lab/Baker Heart and Diabetes Institute
This cartoon schematic shows how scientists hypothesize ExNef promotes neural damage. ExNef enters the neuron, reducing cellular ABCA1. The outcome of reduced ABCA1 is the increase of amyloidogenic proteins within modified lipid rafts of the cell.

Research by Sviridov and his colleagues showed that ExNef, which is absorbed rapidly by neural cells in the lab, reduces the abundance of ATP binding cassette transporter A1, or ABCA1, a membrane protein that functions in the homeostasis and transport of cholesterol and lipids.

The researchers found that when ABCA1 is reduced, cellular cholesterol metabolism is disrupted; lipid rafts, or solid regulatory domains in the cell membrane, are modified and increase in abundance. These changes, a result of the effect of ExNef on ABCA1, promote an accumulation of amyloidogenic proteins. Specifically, the researchers observed an increase in amyloid precursor protein as well as the microtubule-associating protein tau. Both APP and tau play key roles in the pathogenesis of Alzheimer's disease.

The infective mechanism discovered in this study is unique to HIV; however, this research can further our understanding of other illnesses. "In broader terms, this mechanism involving lipid rafts … may apply to non-infectious neurodegenerative diseases, such as Alzheimer's and other pathogens, including SARS-CoV-2, which causes neurological impairment by an unknown mechanism," Sviridov said.

Sviridov and his collaborators now are investigating therapies aimed at mitigating the effects of ABCA1 downregulation and the subsequent increase in lipid raft modification and abundance as a result of ExNef. They hope therapeutic intervention not only will help mitigate the prevalence of HAND but also may work to treat other metabolic disorders.

Enjoy reading ASBMB Today?

Become a member to receive the print edition four times a year and the digital edition weekly.

Learn more
Nicole Lynn

Nicole Lynn holds a Ph.D. from UCLA and is an ASBMB Today volunteer contributor.

Related articles

From the Journals: JBC
Ken Farabaugh
From the journals: JBC
Ken Farabaugh
From the journals: JBC
Ken Farabaugh
From the journals: JBC
Ken Farabaugh
From the journals: JBC
Ken Farabaugh

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

Candy binges can overload your gut microbiome
News

Candy binges can overload your gut microbiome

Nov. 2, 2024

While most Halloween candies contain lots of sugar, some are better for your gut microbiome than others.

Water rescues the enzyme
Essay

Water rescues the enzyme

Oct. 31, 2024

“Sometimes you must bend the rules to get what you want.” In the case of using water in the purification of calpain-2, it was worth the risk.

Virtual issue celebrates water in ASBMB journals
Journal News

Virtual issue celebrates water in ASBMB journals

Oct. 30, 2024

Read a dozen gold open-access articles covering exciting research about the society’s 2024 Molecule of the year.

There are worse things in the water than E. coli
News

There are worse things in the water than E. coli

Oct. 29, 2024

E. coli levels determined whether Olympic swimmers could dive into the Seine this past summer. But are these bacteria the best proxy for water contamination?

Biobots arise from the cells of dead organisms
News

Biobots arise from the cells of dead organisms

Oct. 27, 2024

Given the right conditions, certain types of cells are able to self-assemble into new lifeforms after the organism they were once part of has died.

The shape of molecules to come
News

The shape of molecules to come

Oct. 26, 2024

Researchers explore unique properties of a nanostructure called “switchback DNA” that could have implications in nature and in biomedicine.