Flavivirus Infection and Regulation of Host Immune and Tissue Homeostasis in Insects
Bibliographic record
Abstract
BACKGROUNDFlaviviruses are enveloped single-stranded RNA viruses and major human pathogens.They are responsible for causing outbreaks and therefore they represent a serious health issue worldwide (1).Because of the clinical significance of flaviviruses and the severity of epidemics they cause globally, developing efficient vaccines and drugs is critical for the success of disease control measures.Importantly, many flaviviruses, including Dengue virus (DENV), Japanese Encephalitis virus (JEV), West Nile virus (WNV), Yellow Fever virus (YFV), and Zika virus (ZIKV), are vectored though arthropods (arboviruses), mainly mosquitoes and ticks (2).Although most previous efforts have primarily focused on advancing the design of therapeutic strategies for alleviating the disease symptoms caused by flaviviruses, it is equally significant to also be able to interpret the molecular nature of the interactions that take place between flaviviruses and the insect vector and determine whether these interactions affect pathophysiological processes during infection and transmission.Interactions between mosquito vectors and flaviviruses have been studied in several occasions (3).For instance, ZIKV is mainly transmitted by Aedes aegypti mosquitoes and recent studies have begun to examine vector-virus relationships and transmission dynamics of this virus pathogen (4).Ae. aegypti mosquitoes infected with ZIKV activate the RNA interference (RNAi) mechanism by upregulating several virus-produced short interfering RNAs (siRNAs), piwi-interacting RNAs and microRNAs.Many of the latter are also regulated by DENV and WNVs, but not by the alphavirus Chikungunya, indicating conservation in the mosquito response to flavivirus infection (5).Flavivirus infection in mosquito vectors activates innate immune signaling, which promotes the induction of antiviral response through the production of effector molecules (6).Activation of JAK/ STAT together with Toll signaling elevates the Ae.aegypti resistance to ZIKV infection, silencing the Toll pathway adaptor MyD88 increases DENV infection in the Ae.aegypti midgut, and DENV infection in this mosquito vector decreases the signaling activity of immune deficiency (Imd) pathway (7-9).Interestingly, the secreted protein Vago limits WNV replication in Culex mosquito cells through induction of JAK/STAT signaling (10).Studies in mosquitoes are expected to contribute toward developing efficient procedures for preventing the spread of flaviviruses.Results from research with insect vectors further stress the need for insect immunologists studying antiviral immunity to draw more attention to the outcome of flavivirus infection in insects rather than focusing exclusively on the replication efficacy of the virus.Therefore, this opinion article aims at highlighting recent studies that have started to dissect the interaction between
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".