Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

TSRI researchers develop new method to 'fingerprint' HIV

29.03.2017

HIV is a master of disguise. The virus uses a shield of sugar molecules, called glycans, to hide from the immune system and block antibodies from attacking it.

Now scientists at The Scripps Research Institute (TSRI) have developed a method to analyze the glycan shield on HIV's protective outer glycoprotein, developed as a potential HIV vaccine candidate.


The researchers used their new method to create a map of the surface glycans on an HIV vaccine candidate glycoprotein. (Image from the Paulson Lab.)

Credit: The Scripps Research Institute

With this method, scientists can rapidly create a "fingerprint" of the glycans on the glycoprotein to tell if they are on the right track in developing an effective vaccine.

"The ability to identify the glycan fingerprint on HIV's glycoprotein will help us develop a vaccine that matches what is found on the virus," said James Paulson, Cecil H. and Ida M. Green Chair of Chemistry at TSRI and co-chair of the Department of Molecular Medicine, who led the study published today in the journal Nature Communications.

... more about:
»HIV »HIV vaccine »TSRI »glycan »immune system

Breaking Down HIV's Defenses

With the new method, scientists can finally see which types of glycans make up the glycoprotein--and whether the glycoprotein has any vulnerable holes.

The glycans cover the glycoprotein machinery that HIV uses to enter host cells. The human immune system wants to produce antibodies that bind to the glycoprotein to stop infection, but the glycans block immune cells from seeing their targets and developing useful antibodies.

At TSRI, several research teams are designing HIV vaccines that prompt the body to create rare "broadly neutralizing" antibodies that can actually get around the glycan, or sugar, shield. To do this, they need to introduce the immune system to HIV-like glycoproteins and teach the immune system where the holes in the glycan shield are.

For the new study, the researchers developed a way to figure out the composition of sugars on the glycoprotein. They used enzymes to break the glycoprotein into smaller peptide chunks. Next, the team used a technique called mass spectrometry to analyze these peptides and see if they fell into one of three categories: high-mannose glycans (a type with a specific kind of sugar), complex-type glycans (which are more mature glycans) or sites with no glycans.

While previous HIV studies had distinguished between high-mannose and complex-type glycans, this was the first time scientists could also see the number of glycan-free sites. In fact, the new method has already revealed that the glycoprotein does not have as many holes as many researchers had predicted.

The new method also saves time. Previous studies using mass spectrometry had required researchers to manually analyze the peptide results--a process that could take months. By teaming up with the laboratory of TSRI Professor John Yates, the researchers in this study successfully used a computer algorithm to rapidly analyze results instead.

Study first author Liwei Cao, a research associate in the Paulson laboratory, said speed will come in handy as scientists sort through many HIV vaccine candidates to find the right ones to prevent a wide range of ever-evolving HIV strains.

The next step in this research is to analyze the glycan composition and glycan-free sites on the natural, or "native," form of HIV, not just an HIV-like vaccine candidate. "Then we can see if the fingerprints match up," Paulson said. If they do match, the researchers will know they are on a path to developing a vaccine that can induce useful antibodies.

This new method could also be helpful against viruses with a similar glycoprotein shield, such as influenza, Paulson explained. In fact, the new study included a side project where the researchers successfully tested their method on an influenza protein.

###

In addition to Paulson, Cao and Yates, authors of the study, "Global site-specific N-glycosylation analysis of HIV envelope glycoprotein," were Jolene K. Diedrich, Lin He, Sung-Kyu Robin Park, Ching Yao Su, Claire M. Delahunty, Raiees Andrabi, Javier Guenaga, Erik Georgeson and Michael Kubitz of TSRI; and Daniel W. Kulp, Matthias Pauthner, Devin Sok, Sergey Menis, Yumiko Adachi, Dennis R. Burton and William R. Schief of TSRI and the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center and Consortium.

The study was supported by the National Institutes of Health (grants R01AI113867, UM1 AI100663 and P41 GM103533) and IAVI.

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists--including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine--work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see http://www.scripps.edu.

Media Contact

Madeline McCurry-Schmidt
madms@scripps.edu
858-784-9254

 @scrippsresearch

http://www.scripps.edu 

Madeline McCurry-Schmidt | EurekAlert!

Further reports about: HIV HIV vaccine TSRI glycan immune system

More articles from Health and Medicine:

nachricht Indications of Psychosis Appear in Cortical Folding
26.04.2018 | Universität Basel

nachricht GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Why we need erasable MRI scans

New technology could allow an MRI contrast agent to 'blink off,' helping doctors diagnose disease

Magnetic resonance imaging, or MRI, is a widely used medical tool for taking pictures of the insides of our body. One way to make MRI scans easier to read is...

Im Focus: BAM@Hannover Messe: innovative 3D printing method for space flight

At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.

Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...

Im Focus: Molecules Brilliantly Illuminated

Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.

Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Why we need erasable MRI scans

26.04.2018 | Medical Engineering

Balancing nuclear and renewable energy

26.04.2018 | Power and Electrical Engineering

Researchers 3-D print electronics and cells directly on skin

26.04.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>