Zika and dengue viruses differentially modulate host mRNA processing factors defining its virulence.

Aaron Scholl, Binsheng Gong, Bingjie Li, Tahira Fatima, Nikki Tirrell, Spyros Karaiskos, Maria Rios, Joshua Xu, Sandip De

Abstract read

PubMed Full text at PMC Publisher

In one paragraph

Article in NAR molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Aaron SchollTumor Vaccine and Biotechnology Branch, Division of Cellular Therapy 2, Office of Cellular Therapy and Human Tissue, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, United States.ORCID 0000-0002-9135-6234

Binsheng GongDivision of Bioinformatics and Biostatistics, Office of Research, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, United States.

Bingjie LiTumor Vaccine and Biotechnology Branch, Division of Cellular Therapy 2, Office of Cellular Therapy and Human Tissue, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, United States.

Tahira FatimaTumor Vaccine and Biotechnology Branch, Division of Cellular Therapy 2, Office of Cellular Therapy and Human Tissue, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, United States.

Nikki TirrellAnalytics and Real World Evidence Branch, Division of Analytics and Benefit-Risk Assessment, Office of Biostatistics and Pharmacovigilance, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, United States.

Spyros KaraiskosAnalytics and Real World Evidence Branch, Division of Analytics and Benefit-Risk Assessment, Office of Biostatistics and Pharmacovigilance, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, United States.

Maria RiosOffice of Blood Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, United States.

Joshua XuDivision of Bioinformatics and Biostatistics, Office of Research, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, United States.

Sandip DeTumor Vaccine and Biotechnology Branch, Division of Cellular Therapy 2, Office of Cellular Therapy and Human Tissue, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, United States.ORCID 0000-0002-2859-7203

Funding

Intramural FDA HHS FD999999

6 · The paper itself

Abstract

Changes in global climate have contributed to increased tick and mosquito (vector) populations and subsequent vector-borne flavivirus infections in humans. This increase poses a threat to the safety of human-derived biologics such as cell and gene therapy. We conducted time-course transcriptomic and protein analyses to uncover host molecular factors driving the virulence of Zika virus (ZIKV) and Dengue virus (DENV) in relation to host defense mechanisms, as these viruses have caused recent flavivirus outbreaks. Compared to DENV, ZIKV exhibited stronger virulence and cytopathic effects. RNA-seq analysis revealed differential expression of various cellular factors, including RNA processing factors. Protein analysis showed ZIKV, unlike DENV, degrades nonsense-mediated RNA decay (NMD) factors in host cells, resulting in accumulated host intronic transcripts. We found that active nuclear transport is required for ZIKV replication. From our findings, we hypothesize that ZIKV drives early host cell cytopathy through targeted protein degradation. Studies are underway to develop novel strategies to detect flaviviruses in biologics based on transcriptomics and proteomics.

Identifiers

PMID40919324

DOI10.1093/narmme/ugaf015

PMCPMC12409738

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.