A Brazilian Zika virus isolate suppresses type I interferon to establish a sustained infection in immunocompetent mice
Bibliographic record
Abstract
Abstract Zika virus (ZIKV) is a mosquito-borne pathogen that recently gained international attention following a major epidemic in South and Central America. The most striking aspect of this epidemic was the novel association of ZIKV infection with neurological symptoms, such as fetal microcephaly. In addition, ZIKV may persist in humans for 15- and 42-days post-symptom onset in serum and semen, respectively. Therefore, our objective was to investigate whether recent ZIKV isolates have an enhanced capacity to evade host immunity. To address this objective, we have established an immunocompetent mouse model of ZIKV infection, in which infection with pre-epidemic, early Asian lineage ZIKV isolate (ZIKV-CDN) induces robust type I interferon (IFN) production and prototypical Th1 CD4 and effector CD8 T cell responses. We are now comparing this baseline to the immune response induced by a ZIKV isolate from the Brazilian epidemic (ZIKV-BR). Our data demonstrate a dramatic suppression of type I IFN production during ZIKV-BR infection, which correlates with a severe reduction in the CD8 T cell response. Co-infection reduces the magnitude of the CD8 T cell response when compared to infection with ZIKV-CDN alone, suggesting ZIKV-BR actively interferes with the host immune response. As a result, ZIKV-BR establishes a sustained infection, with high viral loads detected as late as 7 days post-infection. Future studies will aim to determine why less type I interferons are produced, and the impact of ZIKV-BR infection on the CD4 T cell response. Together, our data suggest that contemporary strains of ZIKV have evolved novel ways of countering host immunity, which could explain, at least in part, the increased pathogenicity observed in recent outbreaks.
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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) | 0.001 | 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 | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 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".