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"Scientists discovered that the parasite behind sleeping sickness builds an “invisibility cloak” from special proteins, solving a 40-year mystery about how the deadly disease hides in the body for years."
"... Newly discovered ESB2 proteins may be the reason why. These collectively create a barrier structure called a variant surface glycoprotein (VSG). At the same time, the parasite is also precisely editing its genes to hide inside its host. ..."
From the abstract:
"Antigenic variation is an immune evasion strategy used by pathogens, including Trypanosoma brucei. This parasite expresses a single variant surface glycoprotein (VSG) from a large genetic repertoire, which it periodically switches throughout an infection.
VSGs are co-transcribed with expression-site-associated genes (ESAGs) within a specialized nuclear body, but there is substantial differential expression and the regulatory mechanisms remain unclear.
VSGs are co-transcribed with expression-site-associated genes (ESAGs) within a specialized nuclear body, but there is substantial differential expression and the regulatory mechanisms remain unclear.
Here we applied TurboID-mediated proximity labelling mass spectrometry to map the subnuclear expression-site body (ESB) post-transcriptional network. We identify and characterize three previously undescribed components: ESB-associated protein 1 (ESAP1) and ESB-specific proteins 2 and 3 (ESB2 and 3). These proteins form discreet subnuclear condensates that are developmentally regulated. ESB2 is an active RNA endonuclease that negatively regulates ESAG transcripts. Its recruitment depends on a hierarchy involving VEX2, ESAP1 and ESB3, a constant flux of active transcription and RNA processing, and its own nuclease activity. Overall, we uncover a molecular mechanism that fine-tunes expression of virulence genes through specialized RNA decay in T. brucei."
Parasitic sleeping sickness creates ‘invisibility cloak’ to hide in humans for years "After 40 years, biologists made a breakthrough in understanding the deadly disease."
University of York scientists solve 40-year-old biological mystery behind Sleeping Sickness (original news release) "Scientists at the University of York have cracked a 40-year-old biological cold case by revealing how the parasite that causes Sleeping Sickness stays one step ahead of the human immune system."
Fig. 1: VEX1 and VEX2 PL–MS identified novel ESB-specific, SLAB and NUFIP body components.
The DNA of the the African trypanosome parasite in magenta and it's protective "cloak" in green
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