FEB 28, 2018 10:35 AM PST

New Digital Imaging Analysis Spots HIV Degradation

WRITTEN BY: Kara Marker

A new system that tracks proteins as they come and go in the cell is predicted to help scientists identify therapeutic targets for a multitude of diseases including HIV, cancer, and Alzheimer’s. From the Sanford-Burnham Prebys (SBP) Medical Discovery Institute, scientists focus first on HIV, using the new imaging-based approach to study protein stability.

Scanning electron micrograph of HIV-1 budding from cultured lymphocyte. Multiple round bumps on cell surface represent sites of assembly and budding of virions. Credit: CDC Public Health Image Library

The new “Global Arrayed Protein Stability Analysis" (GAPSA) system is the first cell-based platform that screens for the production and destruction of proteins via high-throughput, genome-scale imaging. It works by identifying circuits in proteins that drive destruction.

In the present study, researchers focused on identifying human proteins degraded by HIV as it promotes its infection process. But in addition to identifying HIV-associated proteins, GAPSA could, in the future, aid in identifying novel therapeutic targets for Alzheimer’s disease, cancer, autoimmune disorders, and infectious disease, including Ebola, influenza, Zika, and more.

GAPSA helped scientists identify proteins in the human host that an HIV accessory protein called Vpu targets as a way to infect the cell and promote replication. Vpu destroys host proteins whose very function is to protect the cell from HIV infection. Vpu also works alongside another HIV accessory protein, Vif, which regulates viral infectivity.

"We selected Vpu as a test case because although some Vpu targets were known, we suspected there were more,” explained senior author Sumit Chanda, PhD. “Indeed, GAPSA was able to pinpoint several host proteins with anti-viral activity that had not been reported in connection with HIV."

In total, Chanda and his team screened 433 interferon-stimulated genes (ISGs), which activate in response to an infection. The screened each against Vpu to “create a more comprehensive list of HIV’s cellular targets,” explained co-author Lars Pache, PhD.

What can identifying Vpu targets with GAPSA do for the anti-HIV agenda? Researchers hope that they can translate their findings into the discovery of new drugs to block Vpu-directed protein destruction, enabling these proteins do their job and protect the body from HIV infection.

“In addition to providing critical knowledge of how cells work, the technology can be applied to identify protein degraders that specifically target disease-causing proteins, which can open new therapeutic opportunities for a multitude of diseases," Chanda explained.

Chanda, Pache, and others hope to continue their research by communicating with scientists in different fields to identify molecular circuits that regulate protein stability in the contexts of different diseases.

“We plan to use the the technology to comprehensively catalog pairs of all human proteins known to regulate degradation and their cellular targets,” Chanda said. “We anticipate that this compendium of activities will expand the therapeutic landscape for many diseases."

The present study was published in the journal Cell Reports.

Sources: Methods in Molecular Biology, Sanford-Burnham Prebys Medical Discovery Institute

About the Author
Master's (MA/MS/Other)
I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
You May Also Like
OCT 23, 2022
Immunology
The Double-Edged Sword of Iron Deficiency
The Double-Edged Sword of Iron Deficiency
Iron is a crucial nutrient. Most of the iron in the body is contained in red blood cells, as part of hemoglobin, which i ...
NOV 01, 2022
Cardiology
Autoimmune Disorders Increase Cardiovascular Risk
Autoimmune Disorders Increase Cardiovascular Risk
People with autoimmune disorders are significantly more likely to develop heart disease compared to the general populati ...
NOV 14, 2022
Drug Discovery & Development
Experimental Opioid Vaccine Could Prevent Overdose Deaths
Experimental Opioid Vaccine Could Prevent Overdose Deaths
Researchers have developed a vaccine that may be able to block the opioid fentanyl from reaching the brain. They note th ...
NOV 20, 2022
Immunology
Mouth Ulcer as First Sign of Monkeypox Infection
Mouth Ulcer as First Sign of Monkeypox Infection
German scientists provided a case study of a 51-year-old patient that highlighted one of the first symptoms a monkeypox- ...
DEC 23, 2022
Drug Discovery & Development
Onchilles Pharma's Newest Drug
Onchilles Pharma's Newest Drug
Onchilles Pharma is a small pharmaceutical company based in San Diego, USA. They work in oncology pharmacy, specifically ...
JAN 19, 2023
Immunology
Surprising Finding Opens Up Novel Treatment Avenues for Lupus
Surprising Finding Opens Up Novel Treatment Avenues for Lupus
Lupus is an autoimmune disease that causes pain, inflammation and tissue damage. It can affect the brain, skin, joints, ...
Loading Comments...