Re-awakening Old Genes To Help In The Fight Against Viruses

A paper published in this week's issue of PLoS Biology describes a study
that has reactivated a dormant gene found in humans and coaxed it - in
tissue culture - to produce an antiviral peptide. Lead scientist Alexander
Cole used aminoglycosides - drugs commonly used to fight bacterial
infections - to trigger the production of the protein, which is encoded by
the dormant human defensin gene that he calls 'retrocyclin'. The
authors hope that this research might ultimately lead to the development
of a treatment that would activate the gene in a person's own cells, for
example, and thereby prevent infection with viruses in the treated tissue.



This research "could make a difference in the fight against viruses such
as HIV," said corresponding author Dr. Cole. "Much more work would be
needed to demonstrate the safety and effectiveness of this approach. We
would certainly have to have human trials, but these findings represent a
promising step in that direction."



Dozens of scientists around the world are looking for ways to prevent the
transmission of viruses such as HIV. Cole and colleagues have previously
discovered that retrocyclin proteins found in some primates appeared to
prevent HIV infections in cell cultures. The same gene exists in humans,
but
because of a mutation that interrupts the gene sequence, it no longer
produces protein.



Now, a collaboration between researchers at UCLA, the Centers for Disease
Control, and Cole's team at the University of Central Florida has found
that restoring the production of retrocyclins prevents HIV entry into
human cells. The scientists have found a way to get the gene to produce
the
retrocyclin and then showed that the retrocyclin appears to prevent the
transmission of HIV in cells cultured in the laboratory. They applied
aminoglycoside antibiotics to vaginal tissues and cervical cells in the
lab and found the antibiotic appears to stimulate those cells and tissues
to
produce retrocyclins on their own.



Cole said he believed there is a possibility the aminoglycoside
antibiotics will be used in a cream or gel format that could someday be a
simple way
to prevent the transmission of HIV. Much more work would be required
before this would be possible, including taking the result in tissue
culture and
showing the same effect in whole organisms.



Funding - This work was supported by grants AI052017 and AI065430 (to
A.M.C) from the National Institutes of Health. The funders had no role in
study
design, data collection and analysis, decision to publish, or preparation
of the manuscript.



Competing interests statement - The authors declare that no competing
interests exist.



Citation:

"Reawakening retrocyclins: ancestral human defensins active against HIV-1."
Venkataraman N, Cole AL, Ruchala P, Waring AJ, Lehrer RI, et al. (2009)

PLoS Biol 7(4):e1000095. doi:10.1371/journal.pbio.1000095


Source
Plos Biology