Osuna, A. | Search bioRxiv

bioRxiv2026

Prevalent phenotypic mutation impairs binding of broadly neutralizing antibodies to influenza hemagglutinin

Mistakes during protein synthesis, such as transcription errors, occur often and lead to non-inheritable amino acid replacements generally known as phenotypic mutations. We recently used a consensus approach in high-throughput sequencing to determine the error landscape for influenza-hemagglutinin mRNA. We found single-site errors to occur with widely different frequencies. Here we show that the most prevalent transcription error encodes a phenotypic mutation that impairs binding of broadly neutralizing antibodies. The error occurs in 0.2-0.5% of mRNA molecules and, consequently, many virions will expose hemagglutinin variants bearing the encoded amino acid replacement. Our results point to a mechanism of antibody evasion, akin to programmed recoding, in which evading mutations are encoded by transcription errors promoted by inheritable RNA sequence/structure patterns.

microbiology↗

bioRxiv2026

Influenza evolution/adaptation samples a highly non-random error landscape for hemagglutinin-encoding RNA

Natural selection acts on diversity generated by errors in the biosynthesis of the genetic material. Previous work has shown, however, that such errors are not necessarily fully random. We have used a model influenza strain and a unique-molecular-identifier-based high-throughput sequencing approach to assess the error landscape for hemagglutinin-encoding RNA. Single-site errors occur at highly variable frequencies, with differences that span several orders of magnitude, plausibly reflecting specific RNA sequence/structure patterns. Remarkably, influenza evolution/adaptation preferentially selects mutations encoded by the higher frequency errors, as shown by analyses of mutations fixed in natural strains over many decades and by analyses of antibody-escape mutations found in laboratory experiments on strains of the 2009 pandemics. Our results support that RNA error landscapes may provide information useful for predicting influenza evolution and point to high-frequency errors encoding antibody-evading mutations as potential contributors to the rapid evolution of influenza viruses.

microbiology↗

bioRxiv2021

First description of Lotmaria passim and Crithidia mellificae haptomonad stage in the honeybee hindgut

The remodelling of flagella into attachment structures is a common and important event in the insect stages of the trypanosomatid life cycle. Among their hymenopteran hosts, Lotmaria passim and Crithidia mellificae can parasitize Apis mellifera, and as a result they might have a significant impact on honeybee health. However, there are details of their life cycle and the mechanisms underlying their pathogenicity in this host that remain unclear. Here we show that both L. passim promastigotes and C. mellificae choanomastigotes differentiate into haptomonad stage covering the ileum and rectum of honeybees. These haptomonad cells remain attached to the host surface via zonular hemidesmosome-like structures, as revealed by Transmission Electron Microscopy. Hence, for the first time this work describes the haptomonad morphotype of these species and their hemidesmosome-like attachment in Apis mellifera, a key trait exploited by other trypanosomatid species to proliferate in the insect host hindgut. Author summaryIn recent years, the mortality of European Honeybees (Apis mellifera) has risen worldwide due to a variety of factors, including their infection by parasites. Former studies have linked the presence of several trypanosomatids species, being Lotmaria passim and Crithidia mellificae the most prevalent ones, with this increase in mortality. Although previous studies have shown that trypanosomatid infection reduces the lifespan of bees, there is little information regarding their development in the gut when honeybees become infected. Here, for the first time we describe the haptomonad morphotype of these two trypanosomatid species in A. mellifera. The most characteristic feature of haptomonads is the extensive remodelling of the flagellum and the formation of junctional complexes at the host gut wall. The presence of this morphotype in the honeybee hindgut increases our understanding of the life cycle of these species and their possible pathogenic mechanisms. We found that they can multiply while attached and that their disposition, covering the hindgut walls, could hinder host nutrient uptake and consequently, represent a pathogenic mechanism itself. This attachment could also be a key stage in the life-cycle to prevent the trypanosomatids leaving the host prematurely, ensuring transmission through infective morphotypes.

pathology↗