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
  • 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
NOV 17, 2019
Health & Medicine
NOV 17, 2019
Tick-Borne Diseases Are Rapidly Rising in the U.S.
Tick-borne diseases have significantly increased in the U.S. in the past few years. In 2016 there were 48,610 reported cases and in 2017 59,349; these...
NOV 17, 2019
Genetics & Genomics
NOV 17, 2019
Increasing Evidence Shows Narcolepsy is an Autoimmune Illness
Narcolepsy is a chronic sleep disorder impacting as many as 200,000 people in the US, and is thought to often go undiagnosed....
NOV 17, 2019
NOV 17, 2019
Dengue Vaccine Reaches the Clinic, with Restrictions
Dengue fever is an unusual virus that presented complications for the recently-developed and first vaccine for the disease....
NOV 17, 2019
Health & Medicine
NOV 17, 2019
Low Number of Vaccine Injury Claims Demonstrate Their Safety
To spread awareness of vaccine safety, New York Times reporters Pam Belluck and Reed Abelson wrote a comprehensive report about vaccine injury claim data....
NOV 17, 2019
NOV 17, 2019
A New Way To Fight Severe Peanut Allergies
Dr. Sandra Lin explains how SLIT is currently being used to treat allergies other than peanuts.    Over 1 million U.S. children have an allergy t...
NOV 17, 2019
Drug Discovery & Development
NOV 17, 2019
Effective Vaccines for Lyme Disease?
Currently, there are no effective vaccines available for the presentation of Lyme disease. The only preventive efforts present includes “guiding&rdqu...
Loading Comments...