Gene duplication and retrotransposition expand antiviral IFITM protein diversity in macaques
Researchers have characterized an expanded set of IFITM antiviral proteins in macaques, finding that gene duplication and retrotransposition produced variants with distinct antiviral activities and regulatory mechanisms. The study examined how canonical and non-canonical macaque IFITM proteins restrict viruses including influenza A, VSV, Sendai virus, and HIV-1. The findings shed light on how evolutionary processes diversify innate immune defenses in primates, with potential implications for understanding antiviral immunity more broadly.
A new preprint study on bioRxiv investigated the functional consequences of an expanded IFITM gene repertoire in macaques, which includes the canonical IFITM1 and IFITM3, a duplicated paralog (IFITM3A), and two retrotransposed copies (IFITM3-R1 and IFITM3-R2). The researchers found that IFITM3A displayed enhanced antiviral activity compared to IFITM3, particularly against vesicular stomatitis virus (VSV) and HIV-1, with specific amino acid substitutions identified as contributing to this enhanced function. In contrast, the retrocopy IFITM3-R1 showed markedly reduced protein expression due to lysosome-dependent degradation driven by a PPxY motif and a unique lysine residue; modifying these elements boosted expression and selectively improved restriction of VSV and influenza A virus. The study also found that while several macaque IFITMs reduced HIV-1 infectivity when present in virus-producing cells, none significantly blocked HIV-1 infection in target cells, and differential incorporation of IFITMs into HIV-1 virions did not consistently predict antiviral potency. Together, the results demonstrate that gene duplication and retrotransposition have generated a functionally heterogeneous antiviral toolkit in macaques, offering new insight into the molecular evolution of innate immunity in primates.
What's missing
As a preprint, this study has not yet undergone formal peer review, so findings should be interpreted with caution. The study does not address whether the expanded IFITM repertoire confers measurable fitness advantages in macaques during natural viral infections in vivo, nor does it examine whether similar retrotransposition events have occurred in other primate lineages beyond macaques.
What different sources said
- bioRxivCenter
Gene duplication and retrotransposition diversify the antiviral repertoire of macaque IFITM proteins
Related
Gut Bacteria Enzyme Found to Break Down Heat-Processed Food Compounds, Producing Novel Biogenic Amines
Researchers have discovered that an enzyme in common gut bacteria can degrade N-epsilon-carboxymethyllysine (CML), a compound formed during thermal food processing, producing previously unknown biogenic amines. The enzyme, ornithine decarboxylase SpeC from enterobacteria, acts on CML and related modified lysine derivatives through a low-level 'underground' catalytic activity. This finding suggests a previously unrecognized communication axis between thermally processed dietary compounds and gut microbial physiology, with potential implications for host health.
Full-Length Gene Sequencing Reveals Two Distinct Bacterial Communities in Black-Legged Ticks Expanding Into Canada
Researchers used Oxford Nanopore full-length 16S rRNA gene sequencing to characterize the microbiome of Ixodes scapularis black-legged ticks collected in Nova Scotia, Canada, distinguishing between tick-adapted bacteria and environmentally acquired bacteria. The study comes as I. scapularis — the primary vector of Lyme disease — is rapidly expanding northward into Canada due to climate change. The findings suggest that environmentally derived bacteria in tick microbiomes are not mere contamination, which has implications for how tick microbiome data is collected and interpreted across surveillance studies.
Study Identifies Metabolic Link Between Cell Envelope Stress and Biofilm Formation in Bacteria
Researchers have discovered that the metabolite acetyl-CoA directly inhibits enzymes that degrade the bacterial signaling molecule c-di-GMP, connecting cell envelope biosynthesis stress to biofilm formation in Pseudomonas aeruginosa. The study found that sub-inhibitory concentrations of antibiotics targeting early peptidoglycan biosynthesis — but not other antibiotic classes — elevate c-di-GMP levels by reducing phosphodiesterase activity, with acetyl-CoA competing for the enzyme active site. Because the relevant enzyme domain is broadly conserved across bacterial species, this checkpoint mechanism may be widespread and could have implications for understanding antibiotic-induced biofilm responses.