Bioinformatic and Functional Analysis of Fowl Adenovirus Genomic Sequences
Bibliographic record
Abstract
Fowl adenoviruses (FAdVs) are the aetoiologic agents of inclusion body hepatitis (IBH), and certain isolates of species Fowl aviadenovirus C are the aetiologic agent of inclusion body hepatitis/hydropericardium syndrome (IBH/HPS). Recombinant fowl adenoviruses have been successfully developed as veterinary vaccine vectors. However, insufficient definitions of the protein-coding and noncoding regions and an incomplete understanding of virus-host interactions limits the progress of next-generation vectors. This work describes the first complete genome sequence of FAdV-4 of species Fowl aviadenovirus C. The protein-coding potential of FAdV-4 was characterized using the Bio-Dictionary-based Gene Finder (BDGF) together with an evaluation of sequence conservation among other FAdV species. Employing these criteria, 46 potential protein-coding ORFs were identified. Of these, 33 and 13 ORFs were assigned high and low protein-coding potential, respectively. Notable putative genes with high protein-coding capacity included the previously unreported fiber 1, hypothetical 10.3K, and hypothetical 10.5K genes. Several of the small ORFs less than 300 nt in length that were assigned low coding potential contributed to upstream ORFs (uORFs) in important mRNAs. Additional work describes the downregulation of surface and total MHC-I (BF2) in FAdV-infected cells. Representative isolates from species Fowl aviadenovirus C, D, and E downregulated cell-surface expression of MHC-I in chicken hepatoma cells at 12 hours post-infection, resulting in approximately 71%, 14%, and 11% of the level of MHC-I on the surface of mock-infected cells, respectively. Further, this work reports that FAdV-9 downregulated surface MHC-I by a mechanism dependent on early transcription unit 1 (FE1) within the left-end terminal genomic region and a lysosomal-dependent mechanism that is encoded outside of FE1 and lead to a reduction of total MHC-I levels. Subsequently, it was determined via mutagenesis of the FAdV-9 molecular clone that the genomic region within FE1 predicted to encode ORF1C contributed to the downregulation of cell surface MHC-I in vitro. Further, it was demonstrated that chickens infected with mutant virus lacking ORF1C shed significantly less virus than chickens infected with wild type FAdV-9. These studies provide important new information about immune evasion of FAdVs and will enhance our understanding of IBH and allow the progress of nextgeneration FAdV-based vector systems.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".