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We may share our ancestry with monkeys and lower primates, but if we could produce one of their proteins, our bodies might be able to effectively fight HIV.

According to research published in the June 2006 issue of the Journal of Immunology, monkeys and lower primates such as the Rhesus macaque produce a type of θ-defensin—an anti-bacterial protein—called retrocyclin, which the HIV-1 virus resists weakly. 

While we long ago lost the ability to produce this protein on our own, the University of Central Florida research team behind this finding has received funding to use it to develop a topical microbicide that could prevent transmission of HIV during intercourse.

“While it is speculative to assert that the loss of retrocyclin might have contributed to humans’ susceptibility to HIV, the use of retrocyclins as topical preventatives might help ‘restore’ humans’ ability to prevent HIV transmission,” said Alexander Cole, study author and microbiology professor at UCF’s Burnett College of Biomedical Sciences, via e-mail.

According to Cole, there is no indication why we lost the ability to produce retrocyclin. Gorillas, chimpanzees and humans have the basic blueprint for retrocyclin in their DNA and are able to transcribe the retrocyclin sequence into RNA. However, a “stop code” prevents our bodies from translating the RNA template into a functional peptide. 

Before stumbling upon retrocyclin, Cole ran the gamut of anti-microbial peptides, throwing each at HIV to test for anti-viral properties. But after chatting with study coauthor Robert Lehrer, a UCLA professor of medicine, the pair decided to try out this non-human peptide. 

When they added retrocyclin to infected cells, the protein potently inhibited the virus.

Other inhibitors have had temporary success with HIV-1, but the virus typically develops an almost complete resistance within a month, while retrocyclin proved effective for nearly 125 days—well beyond the period when the researchers collected their data.

“Retrocyclins appear to act by more than one mechanism of action,” Cole said. “Viruses that have to overcome multiple mechanisms generally have a more difficult time mounting resistance to a drug.” 

Cole added that SIV (Simian Immunodeficiency Virus), the HIV-like disease that lower primates can contract, appears to be resistant to retrocyclin, though he admits he doesn’t know exactly how HIV and SIV differ. 

Nathaniel Landau, a professor at the Salk Institute for Biological Studies, said that it is important not to jump to conclusions about how SIV and HIV evolved to infect their respective hosts.

“It is interesting that humans do not produce this θ-defensin and that some of the primates do, but it is a leap to suggest that that has anything to do with SIV or HIV,” Landau said. “There is no reason to believe that SIV was adapted to be resistant to retrocyclin in monkeys and then that HIV lost that resistance because humans do not make retrocyclin. That is pure speculation, and there’s no evidence to support that.”

The NIH recently granted Cole $4 million for his research, and he is currently working with a colleague at UCF, Henry Daniell, to grow retrocyclin in genetically engineered tobacco plants. Cole said he will work with groups from around the country to develop a topical microbicide that can prevent HIV infection in cervical and vaginal tissue. (Just this past weekend, at the opening of the 16th International AIDS conference, Bill Gates expressed hope that an AIDS prevention breakthrough would come in the form of a microbicide that prevents HIV transmission.)

Landau said he is skeptical of the clinical potential of retrocyclin, noting that the peptide does not inhibit HIV nearly as effectively as other drugs that are being developed. 

However, Cole remains optimistic about the peptides’ potential.

“In preclinical studies, retrocyclins appear safe and efficacious in nearly every cell and tissue system tested,” Cole said. “I am very optimistic that retrocyclins will be ready for studies in primates and early clinical studies in humans within the next few years.”

Originally published August 21, 2006


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