FUNCTIONAL CHARACTERIZATION OF BOVINE HERPESVIRUS MAJOR TEGUMENT PROTEIN VP8
Bibliographic record
Abstract
Bovine herpesvirus (BoHV-1) is an important bovine pathogen. The ul47 gene-encoded VP8 is the most abundant protein of the BoHV-1 virion. VP8 is indispensable for BoHV-1 infection in cattle and a UL47-deleted virus exhibits drastic reduction in replication in tissue culture. The reason for the inability of UL47-deleted virus to replicate in cattle is unknown. Interferons (IFNs) secreted in response to viral infection trigger translocation of signal transducer and activator of transcription (STAT1) to the nucleus for induction of IFN-stimulated genes. We observed that VP8 interacts with STAT1 through two regions, amino acids 259-482 and 632-741. IFN-β production was significantly reduced in BoHV-1- but not in BoHV-1ΔUL47-infected cells. VP8 did not alter STAT1 phosphorylation or degrade STAT1, but inhibited nuclear translocation of STAT1 to reduce IFN-β production. Thus, VP8 plays a vital role in inhibition of IFN-β signaling via interaction and sequestration of STAT1 in the cytoplasm. \n VP8 also interacted with Ataxia telangiectasia mutated (ATM) and Nijmegen breakage syndrome-1 (NBS1), which are critical components in the DNA damage response. Association of VP8 with ATM and NBS1 did not affect ATM, but inhibited NBS1 activation. Consequently, phosphorylation of structural maintenance of chromosome-1 (SMC1), the downstream regulator of the ATM/NBS1 pathway, was abolished. BoHV-1 but not BoHV-1ΔUL47 infection inhibited NBS1 and SMC1 phosphorylation. In addition, VP8 induced apoptosis through caspase-3 activation. Hence, VP8 blocks the ATM/NBS1/SMC1 pathway resulting in induction of apoptosis, which reveals a role of VP8 in the modulation of the DNA damage response.\n We identified heat shock protein-60 (HSP60) as a mitochondrial interacting partner of VP8. VP8 co-localized with HSP60 in the mitochondria. Association of VP8 with mitochondria reduced mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) production. Mitochondrial functions were impaired in BoHV-1- but not in BoHV-1ΔUL47-infected cells. Thus, VP8 might contribute to the deregulation of mitochondrial functions. \n These results demonstrate that VP8 plays a crucial role during BoHV-1 infection by down-regulating IFN-β signaling, inhibiting the DDR pathway and deregulating mitochondrial functions. These functional characteristics of VP8 provide a (partial) explanation for the defective replication of BoHV-1ΔUL47 in cell culture and its lack of virulence in cattle.
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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 | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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".