Journal News

JBC: Targeting semen amyloid fibrils to reduce HIV infectivity

Courtney Chandler
Oct. 1, 2016

The human immunodeficiency virus, which attacks the immune system, affects more than 1.2 million people in the U.S. There aren’t any vaccines or cures. Instead, microbicides are used to help protect against the transmission of HIV from person to person. However, the process of transmission isn’t understood fully and can involve both viral and human factors that promote infection.

Gallic acid, or GA, coats the surfaces of amyloid fibrils in semen to prevent HIV infectivity enhancement and coats the peptide precursors to prevent fibril formation.IMAGE COURTESY OF JOSIE LORICCO

In a recent paper published in the Journal of Biological Chemistry, Nadia Roan of the University of California, San Francisco, and George Makhatadze of Rensselaer Polytechnic Institute described a small molecule that prevents a specific human factor from increasing the ability of HIV to cause infection.

Researchers know that the virus itself has many factors that help it infect new hosts. There are also human factors that play a role in the transmission of HIV and a person’s susceptibility to infection. One of these factors is the ordered accumulations of misfolded proteins called amyloid fibrils. These fibrils occur naturally in human semen and have been shown to increase HIV infectivity and decrease the effectiveness of anti-HIV microbicide treatments.

The infection-promoting fibrils have been observed in the semen of both healthy and HIV-infected men. Therefore, researchers want to identify compounds that disrupt the formation of these fibrils or rid them of their infectivity-enhancing properties and reduce the sexual transmission of the virus through semen.

The investigators, led by graduate student Josie LoRicco of Rensselaer Polytechnic Institute, used a screen of small molecules to identify compounds that altered the properties of specific amyloid fibrils in semen. One molecule that came out of the screen, gallic acid, further proved to be capable of reducing HIV infectivity in the presence of semen. “Gallic acid is a small molecule found naturally in many foods, including grapes and tea,” says Makhatadze.

LoRicco, Roan, Makhatadze and colleagues further investigated gallic acid’s properties. They used atomic force and confocal microscopies in addition to several quantitative assays to characterize the interaction between gallic acid and the fibrils. Surprisingly, gallic acid did not induce disassembly of the fibrils but instead bound to their surfaces.

The investigators conducted biophysical analysis of fibrils’ surface properties to understand the nature of the interaction. They demonstrated that gallic acid limits the ability of semen fibrils to enhance HIV infection by binding to the fibrils’ surfaces and neutralizing their surface charge. Additionally, the gallic acid-coated fibrils prevent the formation of new amyloid fibrils by binding the precursor components and changing their charge characteristics.

“Gallic acid appears to do two things,” explains Makhatadze. “First, it inhibits new fibril formation. Second, it interacts with pre-existing fibrils and renders them incapable of facilitating HIV infectivity.”

The investigators suggest that gallic acid may be a useful addition to multicomponent microbicides that target both viral and human factors involved in the promotion of HIV transmission and infection. Makhatadze suggests that “such combination microbicides will be more effective at preventing transmission compared to single-component microbicides.”

Enjoy reading ASBMB Today?

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

Learn more
Courtney Chandler

Courtney Chandler is a biochemist and microbiologist in Baltimore, Md., and a careers columnist for ASBMB Today.

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

CRISPR epigenome editor offers potential gene therapies
News

CRISPR epigenome editor offers potential gene therapies

April 25, 2025

Scientists from the University of California, Berkeley, created a system to modify the methylation patterns in neurons. They presented their findings at ASBMB 2025.

Finding a symphony among complex molecules
Profile

Finding a symphony among complex molecules

April 23, 2025

MOSAIC scholar Stanna Dorn uses total synthesis to recreate rare bacterial natural products with potential therapeutic applications.

E-cigarettes drive irreversible lung damage via free radicals
Journal News

E-cigarettes drive irreversible lung damage via free radicals

April 17, 2025

E-cigarettes are often thought to be safer because they lack many of the carcinogens found in tobacco cigarettes. However, scientists recently found that exposure to e-cigarette vapor can cause severe, irreversible lung damage.

Using DNA barcodes to capture local biodiversity
ASBMB Annual Meeting

Using DNA barcodes to capture local biodiversity

April 15, 2025

Undergraduate at the University of California, Santa Barbara, leads citizen science initiative to engage the public in DNA barcoding to catalog local biodiversity, fostering community involvement in science.

Targeting Toxoplasma parasites and their protein accomplices
Journal News

Targeting Toxoplasma parasites and their protein accomplices

April 11, 2025

Researchers identify that a Toxoplasma gondii enzyme drives parasite's survival. Read more about this recent study from the Journal of Lipid Research.

Scavenger protein receptor aids the transport of lipoproteins
Journal News

Scavenger protein receptor aids the transport of lipoproteins

April 11, 2025

Scientists elucidated how two major splice variants of scavenger receptors affect cellular localization in endothelial cells. Read more about this recent study from the Journal of Lipid Research.