ArticlemBio2025
Microcephaly protein ANKLE2 promotes Zika virus replication.
Article in mBio, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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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.
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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.
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Who cites it
6 citing papers in PubMed.
- Sequence and structural alignments reveal insights into ANKLE2 evolution and function.Protein science : a publication of the Protein Society · 2026Article
- Zika virus and host protein interactions for understanding molecular mechanisms of pathogenesis and therapeutic development.Frontiers in cellular and infection microbiology · 2026Review
- A novel antiviral role of ankyrin repeat and LEM domain-containing 2 (ANKLE2) in restricting vaccinia virus through barrier to autointegration factor (BAF).Journal of virology · 2025Article
- The Dual Role of A20 (TNFAIP3) in Viral Infection: A Context-Dependent Regulator of Immunity and Pathogenesis.Viruses · 2025Review
- Functional Roles and Host Interactions ofPathogens (Basel, Switzerland) · 2025Review
- Structural elucidation of Langat virus helicase unveils dual-target inhibition for broad-spectrum anti-flaviviruses strategy.Frontiers in cellular and infection microbiology · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Orthoflaviviruses are positive-sense single-stranded RNA viruses that hijack host proteins to promote their own replication. Zika virus (ZIKV) is infamous among orthoflaviviruses for its association with severe congenital birth defects, notably microcephaly. We previously mapped ZIKV-host protein interactions and identified the interaction between ZIKV non-structural protein 4A (NS4A) and host microcephaly protein ankyrin repeat and LEM domain-containing 2 (ANKLE2). Using a fruit fly model, we showed that NS4A induced microcephaly in an ANKLE2-dependent manner. Here, we explore the role of ANKLE2 in ZIKV replication to understand the biological significance of the interaction from a viral perspective. We observe that ANKLE2 localization is drastically shifted to sites of NS4A accumulation during infection and that knockout of ANKLE2 reduces ZIKV replication in multiple human cell lines. This decrease in virus replication is coupled with a moderate increase in innate immune activation. Using microscopy, we observe dysregulated formation of virus-induced endoplasmic reticulum rearrangements in ANKLE2 knockout cells. Knockdown of the ANKLE2 ortholog in
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Registered trials
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.