Nidovirus papain-like proteases antagonize the host innate immune response
Bibliographic record
Abstract
Protein ubiquitination regulates important innate immune responses. Ubiquitin (Ub) can be attached to lysine residues on cellular proteins to promote, among other activities, the innate immune responses of the cell. These pathways can in turn be downregulated by the removal of Ub from cellular proteins by deubiquitinases (DUBs). Viruses of the order Nidovirales have positive-sense, single stranded RNA genomes. Within this order are the families Coronaviridae and Arteriviridae, which include viruses known to cause severe disease in humans and animals, respectively. Members of the families Coronaviridae and Arteriviridae share a common mechanism of gene expression, whereby the viral nonstructural proteins (nsps) are initially expressed as a single polyprotein, which is then cleaved into functional units by papain-like protease (PLP) domains encoded within. Interestingly, while also being necessary for viral replication, a number of Nidovirus PLPs have been shown to remove Ub from host proteins, in order to down-regulate the host innate immune response. Here we present the crystal structure of a Nidovirus PLP in complex with Ub. The structure allowed for the characterization of a Ub-binding interface, and identification of specific residues involved in Ub recognition that are distant from the enzyme active site. The selective inactivation of DUB activity of viral PLP enzymes verses their polyprotein cleavage activity by site directed mutagenesis is allowing us to understand the role of DUB activity in evading innate immune responses of the host, and opens the door for the development of improved live attenuated vaccines against Nidoviruses and other viruses encoding similar dual specificity proteases.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".