---
title: "ANP32 is a conserved host factor for replication in Articulavirales revealed by Tilapia Lake Virus"
id: "biorxiv-20-structures-of-the-tilapia-lake-virus-replication-complex-show-that-anp32-is-a"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-20-structures-of-the-tilapia-lake-virus-replication-complex-show-that-anp32-is-a"
content_type: "clinical_feed_article"
specialty: "General"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.16.751959v1?rss=1"
published_at: "2026-09-17T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# ANP32 is a conserved host factor for replication in Articulavirales revealed by Tilapia Lake Virus
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-20-structures-of-the-tilapia-lake-virus-replication-complex-show-that-anp32-is-a
- **Specialty:** [General](https://medichelpline.com/clinical-feed/general.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.16.751959v1?rss=1)
- **Published At:** 2026-09-17T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study examines the replication complex of Tilapia Lake Virus (TiLV), a segmented negative-strand RNA virus in the Amnoonviridae family within the **Articulavirales** order, using biochemical, biophysical, in vitro reconstitution and single-particle cryo-EM structural approaches. - Authors determined high-resolution structures of complexes formed between the TiLV RNA-dependent RNA polymerase (**TiLV-Pol**) and either tilapia (ti) or human (hu) **ANP32A**, revealing how ANP32 interacts with viral polymerase and nucleoprotein. - The tilapia ANP32 leucine-rich repeat domain stabilizes apo-TiLV-Pol in an **encapsidase** conformation, and this complex recruits a second TiLV-Pol in a **replicase** conformation to form an asymmetric dimer. - The ANP32-stabilized asymmetric TiLV-Pol dimer architecture is strikingly similar to orthomyxovirus replication complexes despite TiLV-Pol being ~40% smaller, indicating structural conservation across distant viruses in the order. - The ANP32 low-complexity acidic region interacts with TiLV nucleoprotein, supporting a conserved role for ANP32 in coordinating ribonucleoprotein assembly during genome replication and encapsidation. - Findings support the interpretation that **ANP32** is an ancient and broadly conserved host factor required for genome replication and encapsidation across the **Articulavirales** order. - Because TiLV is an emerging pathogen causing high mortality in tilapia aquaculture, the structural and interaction data point to tilapia ANP32 modifications as potential avenues to engineer TiLV-resistant fish; specific engineering strategies were not detailed in the source.
## Clinical Analysis & Structured Key Points
Structures of the Tilapia Lake Virus replication complex show that ANP32 is a host factor for replication across the Articulavirales order | bioRxiv Skip to main content New Results Structures of the Tilapia Lake Virus replication complex show that ANP32 is a host factor for replication across the Articulavirales order View ORCID Profile Benoit Arragain , View ORCID Profile Martin Pelosse , View ORCID Profile Stephen Cusack doi: https://doi.org/10.64898/2026.09.16.751959 Benoit Arragain 1 Institute of Science and Technology Austria; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Benoit Arragain Martin Pelosse 2 EMBL Grenoble; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Martin Pelosse Stephen Cusack 3 European Molecular Biology Laboratory Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Stephen Cusack For correspondence: cusack{at}embl.fr Abstract Info/History Metrics Supplementary material Preview PDF Abstract Tilapia Lake Virus (TiLV) is a species in the Amnoonviridae family within the Articulavirales order of nuclear-replicating, segmented, negative-strand RNA viruses. This order also encompasses the well-known, but phylogenetically distant Orthomyxoviridae family that includes influenza and Thogoto viruses. Influenza virus replication, but not Thogoto virus, essentially relies on the host acidic nuclear phosphoprotein 32 (ANP32) to form a functional genome replication complex, which comprises an asymmetric viral polymerase dimer composed of a replicase bridged by ANP32 to an encapsidase. However, remains unclear whether this dependency is conserved in divergent viruses from the same order. Using in vitro reconstitution, biophysical and biochemical analyses and high-resolution structure determination by single-particle cryo-electron microscopy, we investigate the complexes formed between the TiLV RNA-dependent RNA polymerase (TiLV-Pol) and either tilapia (ti) or human (hu) ANP32A. We show that the tiANP32 leucine-rich repeat domain acts as a scaffold that stabilizes apo-TiLV-Pol in an encapsidase conformation. The tiANP32-encapsidase complex is then able to recruit and stabilise a second TiLV-Pol in a replicase conformation. The tiANP32-stabilised asymmetric TiLV-Pol dimer has an architecture that is remarkably similar to its orthomyxovirus replication complex counterpart, despite the 40% smaller size of TiLV-Pol. We also demonstrate that the ANP32 low-complexity acidic region interacts with the TiLV nucleoprotein, consistent with a conserved role in co-ordinating ribonucleoprotein assembly. Overall, our findings suggest that ANP32 is an ancient and likely broadly conserved host factor for viral genome replication and encapsidation across the Articulavirales order. Furthermore, TiLV is an emerging fish pathogen causing high mortality in aquaculture and our results provide insight into tilapia ANP32 modifications that could be used to engineer TiLV-resistant tilapia. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared European Molecular Biology Laboratory, https://ror.org/01zjc6908 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Back to top Previous Next Posted September 17, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Structures of the Tilapia Lake Virus replication complex show that ANP32 is a host factor for replication across the Articulavirales order Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. 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Share Structures of the Tilapia Lake Virus replication complex show that ANP32 is a host factor for replication across the Articulavirales order Benoit Arragain , Martin Pelosse , Stephen Cusack bioRxiv 2026.09.16.751959; doi: https://doi.org/10.64898/2026.09.16.751959 Share This Article: Copy Citation Tools Structures of the Tilapia Lake Virus replication complex show that ANP32 is a host factor for replication across the Articulavirales order Benoit Arragain , Martin Pelosse , Stephen Cusack bioRxiv 2026.09.16.751959; doi: https://doi.org/10.64898/2026.09.16.751959 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8006) Biochemistry (18718) Bioengineering (14854) Bioinformatics (44374) Biophysics (22569) Cancer Biology (19698) Cell Biology (26873) Clinical Trials (138) Developmental Biology (13951) Ecology (20984) Epidemiology (2067) Evolutionary Biology (25420) Genetics (16155) Genomics (23490) Immunology (18687) Microbiology (42428) Molecular Biology (18040) Neuroscience (93379) Paleontology (700) Pathology (2977) Pharmacology and Toxicology (5087) Physiology (8109) Plant Biology (15985) Scientific Communication and Education (2095) Synthetic Biology (4556) Systems Biology (10225) Zoology (2386)
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