Scientists discover HIV efficacy from frog secretions
frog skin could be used as a successful treatment in the fight
against HIV infection, which if developed further, could form an
effective pharmaceutical treatment.
The findings take a unique approach, which could lead to topical treatments for preventing HIV transmission.
HIV research, which has stuttered in recent years, could do with some good news as the emergence of drug resistant strains, rising costs, and soaring incidences worldwide has made the task of developing drug treatments doubly difficult.
In addition, the ability of HIV to remain hidden in cells undetected, avoiding destruction by circulating antibodies and immune system cells may explain why after 20 years a vaccine for this virus still has not been produced.
The scientists, from the Vanderbilt University Medical Centre, have been focusing on the specialised granular glands in the skin that produce and store packets of peptides, small protein-like molecules.
In response to skin injury or alarm, the frog secretes large amounts of these antimicrobial peptides onto the surface of the skin to combat pathogens like bacteria, fungi and viruses.
The team screened 15 antimicrobial peptides from a variety of frog species for their ability to block HIV infection of T cells, immune system cells targeted by HIV.
The Australian red-eyed tree frog, Litoria chloris, had the highest levels of peptides that block HIV infection of all species that the researchers tested
The peptides appeared to selectively kill the virus, with the researchers theorising that the peptides inserted themselves into the HIV outer membrane envelope, creating "holes" that cause the virus particle to fall apart.
"If we are able to learn the mechanisms these peptides are using to kill HIV, it might be possible to make small chemical molecules that achieve the same results," said Derya Unutmaz, associate professor of microbiology & immunology at Vanderbilt University Medical Centre.
"Such chemicals would be more practical as therapeutic microbicides."
What was most fascinating was that the antimicrobial peptides did not harm the T cells at concentrations that are effective against the virus, since HIV's outer membrane is derived from, and therefore essentially identical to, the cellular membrane.
The investigators proposed that the peptides acted selectively on the virus in part because of its small size relative to cells.
"The ability of the peptides to destroy HIV was enticing, but to be really effective as antimicrobial agents, they need to prevent transmission of HIV from dendritic cells to T cells," said Unutmaz.
Dendritic cells are the sentinels of the immune system. They hang out in the mucus-generating surface tissues, scanning for invading pathogens.
In further tests, team member, Scott VanCompernolle, fallowed cultured dendritic cells to capture active HIV. He then incubated the HIV-harboring dendritic cells with antimicrobial peptides, washed the peptides away, and added T cells.
"Normally the dendritic cell passes the virus to the T cell, and we get very efficient infection of the T cell," commented Unutmaz. "But when we treated the dendritic cells with peptides, the virus was gone, completely gone."
The discovery was confusing since the prevailing notion is that HIV captured by dendritic cells is hidden and protected.
The investigators currently are using imaging technologies to test the hypothesis that HIV is actually cycling to the dendritic cell surface.
"We think maybe it's popping its head out, looking around for a T cell, and then going back inside to hide until it cycles out again," Unutmaz said.
This finding is significant as it suggests these peptides could be effective since the virus now has nowhere to hide. If this cycling is really happening, a vaccine could be generated that will target the virus captured by dendritic cells.
The findings are reported this month in the Journal of Virology.
