Recently-Discovered Antiviral Protein Inhibits HIV-1 in Non-Human Primates

A team of scientists led by the University of Colorado Boulder has discovered that a gene called SLFN11 — which encodes a protein known as Schlafen family member 11, or Schlafen11 — may induce a cellular response against infection by viruses including human immunodeficiency virus — 1 (HIV — 1). The research is published in the journal PLoS Pathogens .

Recently-Discovered Antiviral Protein Inhibits HIV-1 in Non-Human Primates

Colorized scanning electron micrograph of HIV — 1, grown in cultured lymphocytes; virions are seen as small spheres on the surface of the cells. Image credit: C. Goldsmith.
The human immune system contains various protein-encoding genes that are able to recognize the foreign signatures of RNA viruses and prevent their replication, providing a genetic line of defense against zoonotic (animal-based) diseases.
HIV — 1, the virus that causes AIDS, is one of several zoonotic retroviruses that has been able to subvert these defenses and adapt to human hosts via mechanisms that are still being studied. HIV — 1 was passed to humans from primates.
In 2012, a University of California San Diego-led team of researchers demonstrated that the SLFN11 gene is capable of limiting HIV — 1 replication early in the virus’s lifecycle, but the mere presence of SLFN11 in humans has not, to date, provided an effective bulwark against the disease.
The new study found that SLFN11’s antiviral potency is highest in non-human primate species such as chimpanzees and orangutans, but less effective in humans and gorillas, indicating that the gene’s effects have become highly species-specific over time when it comes to fighting off HIV — 1.
“The findings suggest that HIV — 1 has been able to take advantage of this relaxed selection in humans,” explained study lead author Alex Stabell, a researcher in the BioFrontiers Institute at the University of Colorado Boulder.
“The immune system contains some of the most rapidly evolving genes in mammalian genomes, and what we are finding is that the immune systems of even very closely-related species, such as humans and chimpanzees, differ in dramatic ways,” added senior author Dr. Sara Sawyer, also from the BioFrontiers Institute.
The team analyzed data from primate genome projects to get a broader picture of the SLFN11 gene’s evolutionary history and compare its antiviral effects in other primate species.
“We examined different versions of this gene in other primate species, looking for positive selection over time,” Stabell said.
“Genes tend to want to be conserved, to stay the same. But a rapidly adapting retrovirus can force their hand.”
The analysis found that over millions of years, the antiviral effectiveness of the SLFN11 gene diverged by species to the point where Schlafen11 proteins encoded by chimpanzees, orangutans, gibbons and marmosets now inhibit HIV — 1 replication far more effectively than those produced by human, gorillas and bonobos.
The researchers also found that SLFN11 can have antiviral effects beyond just HIV — 1.
Even when HIV — 1 is absent from a host’s system, the gene broadly restricts protein production based on non-optimized codons, essentially reprogramming cells to create a general antiviral state.
The findings could provide new avenues of inquiry for future pharmaceutical and gene therapy research centered on HIV — 1.