Hello,

I received this today in my email from "The Center for North American Herpetology" and thought I would share. It is a very interesting article!

Frog Secretions Block HIV Infections

Leigh MacMillan

A new weapon in the battle against HIV may come from an unusual source
–-
tropical frogs. Investigators at Vanderbilt University Medical Center
have discovered that compounds secreted by frog skin are potent blockers of HIV infection.

The findings, reported this month in the Journal of Virology, could
lead to topical treatments for preventing HIV transmission and reinforce the value of preserving the Earth’s biodiversity.

"We need to protect these species long enough for us to understand
their medicinal cabinet," says Louise A. Rollins-Smith, associate professor of microbiology & immunology, who has been studying the antimicrobial defenses of frogs for about six years. Frogs, she explains, have specialized 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.

Rollins-Smith happens to have the laboratory next door to Derya
Unutmaz, associate professor of microbiology and immunology. During a hallway chat one day, the two decided it would be interesting to investigate whether any frog peptides have activity against human viruses, specifically HIV, the focus of Unutmaz’s group.

Postdoctoral fellow Scott E. VanCompernolle 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. He found several that inhibited HIV infection without harming the T cells. The Australian Red-eyed Treefrog, Litoria chloris, had the highest levels of peptides that block HIV infection of all species that the researchers tested. The peptides appear to selectively kill the virus, perhaps by inserting themselves into the HIV outer membrane envelope and
creating "holes" that cause the virus particle to fall apart, Unutmaz
said.

"We like to call these peptides WMDs – weapons of membrane
destruction," Unutmaz quips. It is curious that the antimicrobial peptides do not harm the T cells at concentrations that are effective against the virus, he notes, since HIV’s outer membrane is derived from, and therefore essentially identical to, the cellular membrane. The investigators have proposed that the peptides act 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, Unutmaz said. Dendritic cells, he explains, are the sentinels of the immune system. They hang out in the mucus-generating surface tissues, scanning for invading pathogens. "Their purpose in life is to capture the enemy,
bring it to the lymph node – the command center – and present it to the general, the T cell, to activate a battle plan," Unutmaz says. "It’s a very efficient system that has allowed us to survive many insults, pathogens, and viruses."

But HIV is a wily foe. When it is picked up at the mucosal surface by a
sentinel dendritic cell, it somehow evades destruction. Instead, it hides inside the cell, waiting to invade the T cell with a Trojan Horse-like mechanism. The ability of HIV to remain hidden in the dendritic cell, avoiding destruction by circulating antibodies and immune system cells, "may explain why after 20 years we don’t have a vaccine for this virus," Unutmaz says.

To test the effectiveness of the frog peptides in preventing HIV
transmission, VanCompernolle first allowed 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," Unutmaz says. "But when we treated the dendritic cells with peptides, the virus was gone, completely gone. This was a great surprise."

The finding was puzzling, he explains, 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. If peptide is present outside the cell, "it targets the virus that pops up and kills it." Preliminary experiments suggest that the hypothesis is correct. "This is very exciting, as it suggests that these peptides could be very effective since the virus now has nowhere to hide," Unutmaz says. "And if this cycling is really happening, we may be able to generate a vaccine that will target
virus captured by dendritic cells." The frog peptides are an exceptional tool for probing "what the virus knows about the dendritic cell that we don’t know," Unutmaz added. "How does HIV manage to survive and cycle back and forth to the cell membrane? If we can understand that, we’ll find the gaps, and that will open a whole new universe of
targets for intervention."

The investigators learned this week that the American Foundation for
AIDS Research will fund their continuing quest to understand how the frog peptides kill HIV in dendritic cells. Their plans include imaging how the peptides work, screening additional frog peptides for activity, and testing peptides on a mucosal cell system to study the feasibility of developing them as prophylactics against HIV infection.

"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," Unutmaz says. Such chemicals would be more practical as therapeutic microbicides.

"This study is a great example of how collaboration across disciplines
leads to big discoveries," Unutmaz says. Other members of the department of microbiology and immunology assisted the investigators by providing viruses for testing. The team found that membrane-coated viruses were susceptible to destruction by the frog peptides, but non-coated viruses, such as reovirus and adenovirus, were not affected.

R. Jeffery Taylor, Kyra Oswald-Richter, Jiyang Jiang, Bryan E Youree,
Christopher
R. Aiken and Terence S. Dermody at Vanderbilt are co-authors of the
study. The
research was supported by the National Institutes of Health, the
Elizabeth B.
Lamb Center for Pediatric Research, and the National Science
Foundation.

__________________
.:: Rich ::.

+ Spread The Info

that I svery interesting indeed! thanks for sharing!!

Wow that's great news! I hope they are able to use the frog secretions in humans successfully.

I have another piece of news. For several years herpetologist Adam Britton and other scientists have been working in Australia testing the blood of crocodiles. Crocodiles have a super immune system and they are able to fight off potentially severe bacterial infections quite easily. It's possible that some of our next antibiotics or a similar type of drug might be created out of the research dealing with the crocodiles ability to fight infection.

Rich- we should make a Herps in the news or a Science forum.

__________________
Tricia

I was thinking along the same lines as the croc-blood antibiotics that made a huge news splash a few weeks ago.

__________________
~ Mark

That's really cool. I hope that the frogs they are working with are allright and not threatened like most are becoming.

Mark, there have been news stories leaking out for a few years about the croc blood studies. I also saw a documentory (on Discovery channel? animal planet?) A couple of years ago about it.

Cody, I did a search and the Australian red-eyed tree frog (Litoria chloris) that showed the highest response against the HIV virus is NOT on the endangered or threatened list. However, as scientists discover more and more ways that frogs and other reptiles can protect our health I would hope that this would lead to greater concern over protecting their natural habitats.

Oh, here's another one:
FDA Ok's lizard spit drug for Diabetes

Anyway ... now when we run into "Herp-Phobic" people we can tell them about how frogs, Lizards and crocodiles might help save our lives, help us manage serious diseases, or help cure serious infections.

__________________
Tricia

Hello,

The forum sounds like a good idea. I have also contacted Joe at CNAH to see if I can reprint some of the articles directly on the site. (They have a ton of them!) How does "Herps and Science" sound as a forum name?

__________________
.:: Rich ::.

+ Spread The Info

Sounds great to me Rich. I also hope that Joe lets you reprint some of their articles.

__________________
Tricia

Along the same lines have any break thrus come from sharks for cancer or the like?

hmm I wonder if it would work just to lick the frog, err toad...

__________________
~ Mark