Related Articles

Faster growth with shorter antigens can explain a VSG hierarchy during African trypanosome infections: a feint attack by parasites.
Competition among variants is predictable and contributes to the antigenic variation dynamics of African trypanosomes

RNAs compete to make a coat for parasitic African trypanosomes

A team at the School of Life Sciences, University of Dundee has shown that RNA transcripts from a large gene family compete with each other and that a single active winner emerges.

Scientists in WCAIR  have demonstrated an RNA-based mechanism that allows parasites to survive in their human and animal hosts, expressing unique and switchable surface coats. This antigenic variation enables trypanosomes to continually escape host immune defences.

Several cellular functions depend upon expression of a single uniform type of surface protein or receptor, not just parasitic trypanosomes, the subject of the current study, but also parasites that cause malaria, and the olfactory neurons that sense odours in mammals. Despite intense study, such gene choice mechanisms are not understood in detail in any cell type.

The current paper is published in Nucleic Acids Research. David Horn, Professor of Parasite Molecular biology in the Wellcome Centre for Anti-Infectives Research, said that the findings reveal a key new piece of the Variant Surface Glycoprotein (VSG) gene expression puzzle.

“We previously reported the discovery of ‘VSG exclusion factors’, but something was still clearly missing” he said. “The current study reveals how VSG genes can communicate and compete with each other. VSG genes compete for VSG exclusion factors, which then act to transmit a negative signal to other genes. What is now clear is that the signal is RNA-based”.

Douglas has short dark hair, a short beard and wears round black rimmed glassesDouglas Escrivani (pictured), first author on the paper, said “Singular VSG expression is central to virulence in African trypanosomes. The mechanism we have uncovered allows these parasites to continually switch VSGs surface coats and escape adaptive host immune defences”.

David said that outstanding questions remain, however; “What remains unclear is exactly how VSG exclusion factors generate the negative signal, and how this signal inactivates other VSGs. We hope to tackle these intriguing question in the near future”.

The work was supported by Wellcome, and was greatly facilitated by support from, and access to, the Dundee Imaging Facility and the FingerPrints Proteomics Facility in the School of Life Sciences.