Genetic polymorphisms and antiviral functions of porcine ficolins
Bibliographic record
Abstract
Collagenous lectins, including ficolins (FCN) and mannan binding lectins (MBL) recognize glycan patterns on microbial surfaces, and single nucleotide polymorphisms (SNPs) that alter MBL expression influence susceptibility to various infectious diseases in humans and pigs. The objectives of this thesis were to characterize interactions of porcine FCN with porcine reproductive and respiratory syndrome virus (PRRSV) and to examine the associations of SNPs in FCN and related collagenous lectin genes with susceptibility to PRRSV and other common infectious diseases in pigs. Plasma-purified and recombinant porcine ficolin-[alpha] (FCN-[alpha]) bound to PRRSV particles, neutralized their cytopathic effect and inhibited replication of infectious virions ' in vitro', in a GlcNAc-dependent manner. Fourteen SNPs located in ' MBL's, 'FCN's or 'SP-A' genes and thirteen SNPs located in additional innate immune genes were genotyped in 1283 healthy pigs and 464 pigs diagnosed with common infectious diseases at necropsy using MassARRAY® MALDI-TOF mass spectrometry. Associations with disease diagnoses and with various etiologic agents were evaluated by odds ratio comparisons and a partial least squares (PLS) method of multiple linear regression. When genotype frequencies were compared between diseased and healthy pigs, SNPs found in 'FCN' genes were not significantly associated with disease or etiologic agent. Using a PLS statistical model, the AA genotype of 'FCN'-[alpha] A(671)G was associated with high FCN-[alpha] mRNA expression and decreased risk for K88+ 'E. coli' and porcine circovirus type II (PCV-2) infections. Four SNPs in the 'MBL2' promoter accounted for 41.5% of the variation in hepatic expression of MBL-C mRNA and were associated with enteritis, PCV-2, swine influenza virus (SIV) and 'Mycoplasma' infections. SNPs in 'MBL1' and 'MBL2' accounted for over 40% of the variation in severity of histologically-graded PRRSV-associated pneumonia and the mutant allele of 'MBL2' G(-1081)A was most associated with increased susceptibility to and severity of lung lesions in PRRSV-positive pigs. These studies provide the first evidence for antiviral activity of ficolins but did not find strong associations with disease and polymorphisms in either pig ficolin gene. However, the results suggest that polymorphisms in some collagenous lectins, especially 'MBL2', are markers for susceptibility to pneumonia associated with PRRSV and some other infections in pigs.
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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 | 0.000 |
| 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".