Jason Yeung

@jayeung12.bsky.social

365 Followers 593 Following

MD-PhD candidate @utmbhealth interested in viruses and data science | Former ballet dancer using publicly available dance data for advocacy https://jason-yeung.netlify.app/ https://datapointesguide.com/

Text reading - Broader principle of multimeric polymerase structures dictating possible recombination mechanisms - 'Engineering' demands for greater control over transcription - [[@Viral Genome Principles]] - [[@Segmentation in viruses may allow for more precise gene regulation]] - [[Evolution and Emergence of RNA Viruses]] by [[Edward C. Holmes]] - [[Genome Modularity]] - Demarcation by or acquisition of TRS allows for viral reassortment or new gene formation in a relatively modularized fashion - High fidelity of replication needed to be evolutionarily acquired first before expansion of the genome/elaboration of the TRS subgenomic recombination gene regulation system(?) - How does this work in that bisegmented coronavirus? - [[@Identification and genomic characterization of a novel bisegmented coronavirus in the lesser panda]] - Categorizing everything as the copy choice model is imprecise as there can be many distinct routes to this outcome - [[Viral Recombination Mechanisms]] - Polymerase processivity, fidelity, and speed all relate to backtracking probability - [[Polymerase Backtracking]], [[RdRp Backtracking]]
A picture of organized text. The text reads: - Do homologous, non-homologous, and sgRNA non-homologous recombination all involve the same copy-choice process? - I'm leaning towards some aspects are shared but sgRNA production is generally a more "regulated" process. - Can the frequency of de novo non-sgRNA, non-homologous recombination events be explained by polymerase processivity? - Recombination frequency for SARS-CoV-2 is much higher than other human coronaviruses (MERS-CoV, OC43). Is polymerase processivity correlated with recombination frequency for these viruses? The presence of hotspots already suggests a more complex mechanism than the traditional "fall off, reattach" copy-choice model but this would also. Measurement of processivity is complicated by to processivity-improving proteins nsp7 and nsp8. - Multiple potential mechanisms for promotion of inflammation in nsp15 mutant - Increased dsRNA-induced signaling pathways - Accumulation of DVGs may itself be immunomodulatory - How much of the transcriptomic signal is due to each component? - > "This ~2-3 fold reduction in recombination JFreq indicates that the in vivo environment restricts accumulation of recombination events." - Wonder if this is true in bats as well? Host cells that tolerate high recombination frequencies and multiple coronaviruses could be sites that allow for novel coronavirus emergence through recombination
A picture of organized text. The text reads: - Comparing recombination breakpoints from cell culture vs virions vs *in vivo* vs genomic surveillance has information - A sort of deep mutational scanning dataset for deletions - Comparison of virion enriched sequences and intracellular sequences could support packaging sequence for SARS-CoV-2 (believed to be in nsp12-nsp13) - Terasaki K, Narayanan K, Makino S: **Identification of a 1.4-kb-Long Sequence Located in the nsp12 and nsp13 Coding Regions of SARS-CoV-2 Genomic RNA That Mediates Efficient Viral RNA Packaging**. *Journal of Virology* 2023, **97**:e00659. - Another UTMB lab ☺ - Comparison of cell culture with *in vivo* indicates which are subject to additional (likely immune) selective pressures in hamsters - Comparison of virions with genomic surveillance could indicate which are replication viable and demonstrate sufficient amounts of fitness
A picture of text organized in a list. The text reads: - *__Recombination at poly-U regions still occurred with catalytic inactivation of nsp15__* and *__delDVGs increased while sgmRNA decreased__*. Three potential ways nsp15 catalytic mutants increase non-homologous recombination (not mutually exclusive): - Perhaps this is tied to switch between genome replication and transcription? - > "It is conceivable that the endoU activity of NSP15 may play a role in mediating the template switching between +gRNA and -sgmRNA to give rise to +sgmRNA." - If delDVGs are only generated during genome replication, the increase in delDVGs could be due to a deficit in switching to sgmRNA-production mode. - The lower overall replication for the nsp15 mutant is likely tied to increased immune activation limiting the number of infected cells but the amount of genomic RNA per infected cell could be higher and sgRNA lower. This is suggested by *in vivo* results. - nsp15 catalytic mutants lead to increased dsRNA in highly concentrated puncta - High amounts of dsRNA provide increased opportunities for successful template switches - See the other paper on nsp15 H234A: - Otter CJ, Bracci N, Parenti NA, Ye C, Asthana A, Blomqvist EK, Tan LH, Pfannenstiel JJ, Jackson N, Fehr AR, et al.: **SARS-CoV-2 nsp15 endoribonuclease antagonizes dsRNA-induced antiviral signaling**. *Proceedings of the National Academy of Sciences* 2024, **121**:e2320194121. - These findings may tie in with the SARS-CoV-2 polymerase backtracking story that is developing for coronavirus recombination. - Poly-U tracts and induction of polymerase backtracking have been linked for other RNA polymerases. - Theoretically, anything that could cause polymerase backtracking (poly-U, TRS secondary structures, nucleotide antivirals) has some probability of producing a recombinant viral RNA. Hence why abolishing nsp15 endoU does not get rid of the poly-U enriched pattern
A 3D rendering of a red crab (the mascot for the programming language Rust) with a lit cigarette in one of its claws. Text on a blue background reads "> DAY 7 OF LEARNING RUST".
A banner with an anthropomorphic rendering of a virus with a mask and fedora in front of a purple gradient. The text reads Long COVID's Viral Persistence Hypothesis: Scientific Sticking Points - Challenges creating translational long COVID models. By Jason Yeung @jayeung12.
A picture of a cracked, ceramic brain with viruses spilling out of it. Text says Viruses in the Brain Part I: Complement. How viruses change our thinking and feeling. Written by Jason Yeung