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New University research could help design better HIV vaccine

By Irene Park, For the Daily
Published July 25, 2014

Sunday, a research team headed by Wei Cheng, associate professor of pharmaceutical sciences and faculty member at the College of Pharmacy, published a study in the online journal Nature Nanotechnology showing that HIV viruses differ from one another in their protein composition.

This affects how infectious each virus is to its host cell, and their finding could help in designing better HIV vaccines.

HIV infection is known to cause AIDS, which currently affects about 1.1 million people in the United States and 33.4 million people worldwide, according to statistics from the World Health Organization. It was responsible for the deaths of 1.5 million people worldwide in the year 2013 alone, according to statistics from the Foundation for Aids Research.

Current treatments that are used to treat HIV infection suppress HIV and can delay AIDS-related illnesses, but they do not fully eradicate the virus.

Cheng said the differences in protein composition his team discovered in the HIV viral population was primarily significant to the effectiveness of vaccines because the proteins on the surface of the virus are essential in its ability to attack host cells in the body and also influence how infectious the virus is.

“If the virus has more of the proteins, then it is more infectious, which means we end up with a spectrum (of infectiousness),” he said. “This could have important implications particularly in vaccine design. In vaccines, you want to mimic the viruses closely so the immune system can respond to viruses that are highly infectious, not mediocre ones.”

The concept of differences in the viral population isn’t new — previous works have shown the heterogeneity at the sequence level — but detecting heterogeneity in viral proteins has been a challenge due to technical limitations.

To address this technical issue, Cheng’s research team used a technique called optical tweezers. Optical tweezers consist of a carefully aligned laser beam that is focused at the center of a microfluidic chamber filled with a solution containing nano-scale structures, such as viruses.

Because particles in a solution move in a random motion, studying them has been difficult because while the particles are moving, it is difficult to manipulate them for an experiment. Optical tweezers trap these particles and restrict their movements by utilizing the electric field of the laser beam, which induces polarity in the viruses and ‘traps’ them in the focus of the laser beam because polar molecules are attracted towards the brighter regions of the laser beam.

Optical tweezers have been used to study tobacco mosaic viruses before, but this study represents the first successful demonstration of using optical tweezers to study an animal virus. Studying animal viruses with optical tweezers was previously unsuccessful, particularly because of the shape and smaller size of the animal viruses, which interferes with the effects of the polarity.

To overcome these two problems, Cheng’s team had to build instruments that improved the alignment of the laser beam, which is critical for the success of optical tweezers.

“This type of instrument is not commercially available,” Cheng said. “Commercial instruments do not have the sensitivity that we need. We basically (built) it ourselves.”

Once the optical tweezers technique was improved, Cheng’s team was able to successfully trap the HIV virus and could analyze the viruses one at a time.

The team used a technique called two-photon fluorescence microscopy. The technique involves exciting a fluorescent molecule with two photons and then measuring the fluorescence intensity. The fluorescence intensity values are then used to estimate the number of proteins that are labeled with fluorophores in a single HIV virus.

The team dubbed this quantitative technique “virometry,” which allows the researchers to measure and estimate multiple parameters, including number of proteins, in a single virus.

Cheng noted that the improved optical tweezers technology coupled with two-photon fluorescence microscopy could be applied to other research areas.

“This technique can be applied to studying other viruses and nanoparticles,” he said. “Our department is interested in using nanoparticles as a carrier to deliver drugs (to patients).”


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