The Tanapoxvirus 15L Protein Is a Virus-Encoded Neuregulin That Promotes Viral Replication in Human Endothelial Cells
Bibliographic record
Abstract
Studies on large double-stranded DNA (dsDNA) viruses such as poxviruses have been helpful in identifying a number of viral and cellular growth factors that contribute to our broad understanding of virus-host interaction. Orthopoxviruses and leporipoxviruses are among the most studied viruses in this aspect. However, tanapoxvirus (TPV), a member of the genus Yatapoxvirus, still remains largely unexplored, as the only known hosts for this virus are humans and monkeys. Here, we describe the initial characterization of an epidermal growth factor (EGF)-like growth factor mimicking human neuregulin from TPV, expressed by the TPV-15L gene. Assays using a baculovirus-expressed and tagged TPV-15L protein demonstrated the ability to phosphorylate neuregulin receptors. Neuregulins represent a large family of EGF-like growth factors that play important roles in embryonic endocardium development, Schwann and oligodendrocyte survival and differentiation, localized acetylcholine receptor expression at the neuromuscular junction, and epithelial morphogenesis. Interestingly, certain neuregulin molecules are able to target specific tissues through interactions with heparin sulfate proteoglycans via an immunoglobulin (Ig)-like domain. Analyses of TPV-15L revealed no Ig-like domain, but it retains the ability to bind heparin and phosphorylate neuregulin receptors, providing compelling evidence that TPV-15L is a functional mimetic of neuregulin. TPV-15L knockout virus experiments demonstrate that the virus replicates in human umbilical vein endothelial cells less efficiently than wild-type TPV-Kenya, indicating that this is a nonessential protein for virus viability but can serve a stimulatory role for replication in some cultured cells. However, the precise role of this protein in host-virus interaction still remains to be deduced.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".