The GP2a 91/97/98 amino acid substitutions play critical roles in determining PRRSV tropism and infectivity but do not affect immune responses
Bibliographic record
Abstract
and are commonly used for PRRS vaccine development. However, currently prevalent PRRSV isolates display different Marc-145 cell tropism while the exact determinant is not clarified yet. In this study, we identified for the first time that the 91/97/98 amino acid (aa) substitutions in GP2a of PRRSV play critical roles in determining Marc-145 adaptation. Specifically, multiple series of chimeric viruses were constructed based on four PRRSV infectious clones including Marc-145 adaptive HP-PRRSV-2 strain and Marc-145 non-adaptive NADC34-like PRRSV-2, NADC30-like PRRSV-2, and PRRSV-1 strains. The GP2a 91/97/98 aa substitutions are a sufficient and necessary determinant in NADC34-like and NADC30-like PRRSV-2, a sufficient but not necessary determinant in HP-PRRSV-2, a necessary but not sufficient determinant in PRRSV-1, respectively. In addition, the GP2a substitutions also influenced PRRSV infectivity in PAMs and piglets. Noticeably, the GP2a substitutions did not significantly affect the levels of neutralizing antibodies, porcine T follicular helper (Tfh) cells, and PRRSV-specific IFNγ secreting cells. Overall, our results not only provide new insights into PRRSV tropism and infectivity but also will facilitate PRRS vaccine development. IMPORTANCE: . Clarifying the exact determinant of PRRSV tropism is crucial for PRRSV isolation and vaccine development. By constructing chimeric viruses based on four representative PRRSV infectious clones, we identified for the first time that the 91/97/98 amino acid substitutions in GP2a play critical but distinct roles in determining Marc-145 cell tropism for different PRRSV strains. The GP2a 91/97/98 amino acid substitutions also affect PRRSV infectivity in PAMs and piglets but do not influence immune responses. This study not only deciphers an exact determinant of PRRSV tropism and infectivity but also has guiding significance for PRRS vaccine development.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".