Evidence map›Paper›PMID 35285683›Full record

ArticleJournal of virology2022

VP4 Is a Determinant of Alpha-Defensin Modulation of Rotaviral Infection.

Ciara T Hu, Karina Diaz, Linda C Yang, Anjali Sharma, Harry B Greenberg, Jason G Smith

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Journal of virology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 31% of its field
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

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Ciara T HuDepartment of Microbiology, University of Washington School of Medicinegrid.471394.c, Seattle, Washington, USA.ORCID 0000-0003-0160-1708
Karina DiazDepartment of Microbiology, University of Washington School of Medicinegrid.471394.c, Seattle, Washington, USA.ORCID 0000-0002-4215-242X
Linda C YangDepartment of Microbiology, University of Washington School of Medicinegrid.471394.c, Seattle, Washington, USA.
Anjali SharmaDepartment of Microbiology, University of Washington School of Medicinegrid.471394.c, Seattle, Washington, USA.
Harry B GreenbergDepartment of Medicine and Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, California, USA.ORCID 0000-0002-2128-9080
Jason G SmithDepartment of Microbiology, University of Washington School of Medicinegrid.471394.c, Seattle, Washington, USA.ORCID 0000-0001-6727-5269
University of Washington · USStanford Medicine · US

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Washington National Primate Research CenterP51OD010425 · OD · UNIVERSITY OF WASHINGTON · PI Mari Ostendorf · 2012 to 2026
$201.8M
Institute of Translational Health SciencesUL1TR000423 · NCATS · UNIVERSITY OF WASHINGTON · PI DISIS, MARY L. · 2012 to 2016
$49.4M
Anti-viral Mechanisms of DefensinsR01AI104920 · NIAID · UNIVERSITY OF WASHINGTON · PI MCKENNA, ROBERT, SMITH, JASON G · 2014 to 2023
$6.1M
Viral Pathogenesis Training ProgramT32AI083203 · NIAID · UNIVERSITY OF WASHINGTON · PI BLOOM, JESSE D, LAGUNOFF, MICHAEL · 2009 to 2023
$2.7M
Regulation of Rotavirus Replication, Virulence, and Host Range Restriction by the Innate Immune SystemR01AI125249 · NIAID · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI GREENBERG, HARRY BERNARD · 2017 to 2021
$2.1M
Defining defensin-mediated inhibitionand enhancement of rotavirus infectionF30AI140620 · NIAID · UNIVERSITY OF WASHINGTON · PI DIAZ-DAVIS, KARINA · 2019 to 2021
$125k
Azure Sapphire BioimagerS10OD026741 · OD · UNIVERSITY OF WASHINGTON · PI SMITH, JASON G · 2019 to 2019
$76k
NCATS NIH HHS UL1 TR000423NCI NIH HHS P30 CA015704NIAID NIH HHS F30 AI140620NIAID NIH HHS R01 AI104920NIAID NIH HHS R01 AI125249NIAID NIH HHS T32 AI083203NIH HHS P51 OD010425NIH HHS S10 OD026741
6 · The paper itself

Abstract

Fecal-oral pathogens encounter constitutively expressed enteric alpha-defensins in the intestine during replication and transmission. Alpha-defensins can be potently antiviral and antibacterial; however, their primary sequences, the number of isoforms, and their activity against specific microorganisms often vary greatly between species, reflecting adaptation to species-specific pathogens. Therefore, alpha-defensins might influence not only microbial evolution and tissue tropism within a host but also species tropism and zoonotic potential. To investigate these concepts, we generated a panel of enteric and myeloid alpha-defensins from humans, rhesus macaques, and mice and tested their activity against group A rotaviruses, an important enteric viral pathogen of humans and animals. Rotaviral adaptation to the rhesus macaque correlated with resistance to rhesus enteric, but not myeloid, alpha-defensins and sensitivity to human alpha-defensins. While mouse rotaviral infection was increased in the presence of mouse enteric alpha-defensins, two prominent genotypes of human rotaviruses were differentially sensitive to human enteric alpha-defensins. Furthermore, the effects of cross-species alpha-defensins on human and mouse rotaviruses did not follow an obvious pattern. Thus, exposure to alpha-defensins may have shaped the evolution of some, but not all, rotaviruses. We then used a genetic approach to identify the viral attachment and penetration protein, VP4, as a determinant of alpha-defensin sensitivity. Our results provide a foundation for future studies of the VP4-dependent mechanism of defensin neutralization, highlight the species-specific activities of alpha-defensins, and focus future efforts on a broader range of rotaviruses that differ in VP4 to uncover the potential for enteric alpha-defensins to influence species tropism.

Indexed as

alpha-DefensinsRotavirusRotavirus InfectionsAnimalsHumansIntestine, SmallMacaca mulattaMiceViral Structural Proteinsalpha-DefensinsViral Structural Proteinsdefensinsenteric virusesrotavirusviral immunity

Identifiers

PMID35285683
PMCPMC9006894
OpenAlexW4220704735

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.