Antiviral Protein Inhibits HIV in Certain Primates
Gene may induce a broad-spectrum cellular response against infectious diseases.
The protein-coding gene Schlafen11 (SLFN11) may induce a broad-spectrum cellular response against HIV.
In a study published in PLOS Pathogens, investigators found that SLFN11’s antiviral potency is highest in non-human primate species—–such as orangutans and chimpanzees––but less effective in humans and gorillas.
The results of the study indicate that over time, the effects of SLFN11 have become highly species-specific when fighting HIV, according to the authors.
“The finding suggest that HIV-1 has been able to take advantage of this relaxed selection in humans,” said lead author Alex Stabell.
Prior research conducted in 2012 demonstrated the capability of SLFN11 to limit HIV replication early on in the virus’ lifecycle. However, in humans, SLFN11 has not demonstrated efficacy against the disease.
“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,” said senior author Sara Sawyer.
In the study, the investigators analyzed data from primate genome projects across the country to get a broader picture of the 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 results of the analysis showed that over the course of millions of years, the antiviral efficacy of the gene diverged by species, to the point where the SLFN11 proteins encoded by chimpanzees, orangutans, gibbons, and marmosets, now inhibit HIV replication significantly more effectively than those produced by humans, gorillas, and bonobos.
Additionally, the findings showed SLFN11 can have antiviral effects beyond just HIV. According to the authors, even when HIV is absent from the host’s system, the gene broadly restricts protein production based on non-optimized codons. Meaning, the cells are reprogrammed to create a general antiviral state.
The findings may aid in future HIV-based pharmaceutical and gene therapy research, the authors concluded.