Evidence map›Paper›PMID 40060519›Full record

ArticlebioRxiv : the preprint server for biology2025

Host genotype and sex shape influenza evolution and defective viral genomes.

Rodrigo M Costa, Lehi Acosta-Alvarez, Kaili Curtis, Kort Zarbock, Justin Kelleher, Bhawika S Lamichhane, Andrew L Valesano, William J Fitzsimmons, Adam S Lauring, Jon Seger and 2 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 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

5 · Who and what money

Authors and funding

12 authors.

Rodrigo M CostaSchool of Biological Sciences, University of Utah, Salt Lake City, UT, USA.ORCID 0009-0007-8722-1090
Lehi Acosta-AlvarezSchool of Biological Sciences, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0002-2890-4947
Kaili CurtisSchool of Biological Sciences, University of Utah, Salt Lake City, UT, USA.ORCID 0009-0006-9922-2499
Kort ZarbockSchool of Biological Sciences, University of Utah, Salt Lake City, UT, USA.
Justin KelleherSchool of Biological Sciences, University of Utah, Salt Lake City, UT, USA.ORCID 0009-0003-9545-7678
Bhawika S LamichhaneDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-8795-7053
Andrew L ValesanoDepartment of Internal Medicine and Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-3649-8352
William J FitzsimmonsDepartment of Internal Medicine and Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-0997-1108
Adam S LauringDepartment of Internal Medicine and Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-2906-8335
Jon SegerSchool of Biological Sciences, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0001-5324-4840
Frederick R AdlerSchool of Biological Sciences, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0002-9022-3157
Wayne K PottsSchool of Biological Sciences, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0003-4137-0326

Funding

The role of sex in the evolution and spread of virulent infectious diseaseR01GM109500 · NIGMS · UNIVERSITY OF UTAH · PI ADLER, FREDERICK R., POTTS, WAYNE K. · 2013 to 2016
$1.6M
NIGMS NIH HHS R01 GM109500
6 · The paper itself

Abstract

Viral evolution during initial pandemic waves favors mutations that enhance replication and transmission over antigenic escape. Host genotype and sex strongly shape this early adaptation, yet their individual and combined effects remain unclear. We experimentally adapted influenza A virus to male and female BALB/c and C57BL/6 mice, generating 28 independent lineages, and employed a novel "rolling sphere" approach to identify mutational hotspots in three-dimensional protein structures. In BALB/c mice, adaptation favored nonsynonymous substitutions linked to increased virulence, including a hemagglutinin variant exclusively fixed in female lineages. It also revealed the first demonstration of sex-dependent selection shaping a viral protein interface. In female-adapted viruses, substitutions disrupting a key NS1 dimerization motif converged on a single residue, while in male-adapted viruses, they were dispersed across the same interface. Conversely, adaptation to C57BL/6 resulted in fewer substitutions but promoted defective viral genome formation, leading to reduced cytopathic effect and attenuated virulence. This provides the first

Identifiers

PMID40060519
PMCPMC11888471

What OpenQuestion holds

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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.