Genetic or antibiotic prevention for HIV?

Increasingly, researchers are investigating genetic fixes for otherwise intractable conditions.  For example, see the recent blog entry A genetic fix for obesity?  Now, a possible genetic fix is suggested that addresses HIV, a fix that undoes an ancient mutation present in humans.   

The work is reported in a recent online publication Reawakening Retrocyclins: Ancestral Human Defensins Active Against HIV-1.  The good news is that primates including us humans have a gene that produces retrocyclin, antiviral peptide proteins in the defensin family of proteins.  Retrocyclin is a powerful anti-viral substance and “was recently shown to strongly inhibit HIV entry into human cells by blocking the interaction of viral proteins with their cellular receptors(ref).”  The bad news is that way back in evolutionary history our branch of primates, including gorillas and chimps, experienced a  nonsense mutation” in the retrocyclin gene, so it fails to do its job and produce the retrocyclin proteins.  A nonsense mutation is one where a codon encoding an amino acid is changed into a premature stop codon.  This means the protein-making machinery in the cell ribosomes reading mRNA instructions as if they were on a tape stops before it should resulting in an incomplete protein being made or no protein at all.  

The research challenge was to see if repairing the 7 million-year old nonsense mutation in the human retrocyclin gene could restore retrocyclin production and block entry of HIV into human cells like it does in Old World monkeys. “To determine whether human cells have retained the capacity to make retrocyclin protein, Venkataraman et al. corrected the premature stop codon mutation in a copy of the human retrocyclin gene. Next, they inserted the corrected gene into human promyelocytic cells, and looked to see if protein was produced from the gene. They found that cells harboring the corrected gene could make a protein similar to the monkey version of retrocyclin. But could human retrocyclin block HIV infection? Indeed, extracts made from cells containing the corrected gene could reduce HIV growth, and so could the retrocyclin protein purified from these extracts. Collectively, these results suggest that human cells have a potentially important—but latent—mechanism to protect against HIV(ref).” 

So, there is a possibility that a genetic fix could be created to mobilize retrocyclin to protect against HIV.  But the researchers identified an alternative and much easier approach, and that is to use aminoglycosides instead to override the erroneous stop signals in human retrocyclin protein production. “An aminoglycoside is a molecule composed of a sugar group and an amino group.  Several aminoglycosides function as antibiotics that are effective against certain types of bacteria. They include amikacin, arbekacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, rhodostreptomycin, streptomycin, tobramycin, and apramycin(ref).”  Aminoglycosides “– don’t block protein creation in human cells but cause ribosomes to make occasional errors—like missing stop codons. The authors found that treating human cells with aminoglycosides allowed the cells to make retrocyclin at sufficiently high levels to inhibit infection by HIV(ref).”

Hmm.  What this seems to say is that taking one or several of those antibiotics might help protect against HIV infection.  The research says “– we exploited the ability of aminoglycoside antibiotics to read-through the premature termination codon within retrocyclin transcripts to produce functional peptides that are active against HIV-1(ref).”  One possibility would be to make topical creams containing such antibiotics to inhibit sexual transmission of HIV.  Of course there are likely to be other disease risks associated with ignoring protein-making stop instructions and taking these antibiotics.  In any event, human activation of retrocyclin seems to be a promising avenue of research for prevention of HIV infections and AIDS.  If it can be done safely and economically, tens of millions of lives and billions or trillions of dollars could be saved.

About Vince Giuliano

Being a follower, connoisseur, and interpreter of longevity research is my latest career, since 2007. I believe I am unique among the researchers and writers in the aging sciences community in one critical respect. That is, I personally practice the anti-aging interventions that I preach and that has kept me healthy, young, active and highly involved at my age, now 93. I am as productive as I was at age 45. I don’t know of anybody else active in that community in my age bracket. In particular, I have focused on the importance of controlling chronic inflammation for healthy aging, and have written a number of articles on that subject in this blog. In 2014, I created a dietary supplement to further this objective. In 2019, two family colleagues and I started up Synergy Bioherbals, a dietary supplement company that is now selling this product. In earlier reincarnations of my career. I was Founding Dean of a graduate school and a full University Professor at the State University of New York, a senior consultant working in a variety of fields at Arthur D. Little, Inc., Chief Scientist and C00 of Mirror Systems, a software company, and an international Internet consultant. I got off the ground with one of the earliest PhD's from Harvard in a field later to become known as computer science. Because there was no academic field of computer science at the time, to get through I had to qualify myself in hard sciences, so my studies focused heavily on quantum physics. In various ways I contributed to the Computer Revolution starting in the 1950s and the Internet Revolution starting in the late 1980s. I am now engaged in doing the same for The Longevity Revolution. I have published something like 200 books and papers as well as over 430 substantive.entries in this blog, and have enjoyed various periods of notoriety. If you do a Google search on Vincent E. Giuliano, most if not all of the entries on the first few pages that come up will be ones relating to me. I have a general writings site at www.vincegiuliano.com and an extensive site of my art at www.giulianoart.com. Please note that I have recently changed my mailbox to vegiuliano@agingsciences.com.
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