Evidence map›Paper›PMID 33232376›Full record

ArticlePLoS pathogens2020

In vitro and in vivo characterization of a recombinant rhesus cytomegalovirus containing a complete genome.

Husam Taher, Eisa Mahyari, Craig Kreklywich, Luke S Uebelhoer, Matthew R McArdle, Matilda J Moström, Amruta Bhusari, Michael Nekorchuk, Xiaofei E, Travis Whitmer and 25 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

29 citing papers in PubMed, 36 citations in OpenAlex.

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  11. CD8Science advances · 2024
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  12. Evolution of theVirus evolution · 2024
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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

35 authors at 7 institutions in 2 countries.

Husam TaherVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
Eisa MahyariVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.ORCID 0000-0002-5613-3131
Craig KreklywichVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
Luke S UebelhoerVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
Matthew R McArdleVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
Matilda J MoströmTulane National Primate Research Center, Tulane University, Covington, Louisiana, United States of America.ORCID 0000-0001-7261-6638
Amruta BhusariVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
Michael NekorchukVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
Xiaofei EDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.ORCID 0000-0001-9520-2040
Travis WhitmerVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.ORCID 0000-0001-9321-0637
Elizabeth A ScheefTulane National Primate Research Center, Tulane University, Covington, Louisiana, United States of America.ORCID 0000-0002-4209-0409
Lesli M SpreheTulane National Primate Research Center, Tulane University, Covington, Louisiana, United States of America.
Dawn L RobertsDivision of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.ORCID 0000-0002-8411-646X
Colette M HughesVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
Kerianne A JacksonVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.ORCID 0000-0002-7131-3958
Andrea N SelsethVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.ORCID 0000-0001-9536-463X
Abigail B VenturaVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
Hillary C Cleveland-RubeorVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.ORCID 0000-0002-0054-0854
Yujuan YueCenter for Comparative Medicine and Department of Medical Pathology, University of California, Davis, California, United States of America.
Kimberli A SchmidtCenter for Comparative Medicine and Department of Medical Pathology, University of California, Davis, California, United States of America.ORCID 0000-0003-4927-6991
Jason ShaoStatistical Center for HIV/AIDS Research and Prevention, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.ORCID 0000-0003-0830-0211
Paul T EdlefsenStatistical Center for HIV/AIDS Research and Prevention, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Jeremy SmedleyOregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, United States of America.ORCID 0000-0003-3369-4662
Timothy F KowalikDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.ORCID 0000-0001-6096-3018
Richard J StantonDivision of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom.ORCID 0000-0002-6799-1182
Michael K AxthelmOregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, United States of America.ORCID 0000-0002-1984-5906
Jacob D EstesVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
Scott G HansenVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
Amitinder KaurTulane National Primate Research Center, Tulane University, Covington, Louisiana, United States of America.
Peter A BarryCenter for Comparative Medicine and Department of Medical Pathology, University of California, Davis, California, United States of America.ORCID 0000-0002-7982-674X
Benjamin N BimberVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.ORCID 0000-0001-8092-3080
Louis J PickerVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.ORCID 0000-0003-0546-398X
Daniel N StreblowVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
Klaus FrühVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
Daniel MalouliVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.ORCID 0000-0003-1287-7283
Oregon Health & Science University · USOregon National Primate Research Center · USTulane University · USUniversity of California, Davis · USCardiff University · GBFred Hutch Cancer Center · USUniversity of Massachusetts Chan Medical School · US

Funding

Upgrade of confocal microscopy at the Oregon National Primate Research CenterP51OD011092 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Bonnie J. Nagel · 2012 to 2026
$203.9M
National Institute on Aging (NIA) ColonyP51OD011107 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Simon J. Atkinson · 2012 to 2026
$191.5M
Tulane NPRC SPF Sheltered Outdoor Enclosure ExpansionP51OD011104 · OD · TULANE UNIVERSITY OF LOUISIANA · PI L Lee HAMM · 2012 to 2026
$142.4M
Virology CoreP01AI129859 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI Sallie R. Permar · 2019 to 2026
$31.0M
Phase 2 Enhancement of Outdoor Group Housing for U42 SPF 9 Rhesus MacaquesU42OD023038 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Andrew Haertel · 2016 to 2026
$21.9M
Virology and Immunology MonitoringP01AI094417 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI PICKER, LOUIS J. · 2011 to 2016
$20.5M
Virology and Vector Production Core CU19AI128741 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI STREBLOW, DANIEL N · 2017 to 2021
$11.8M
Role of Memory T Cell Dynamics in SIV InfectionR37AI054292 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI PICKER, LOUIS J. · 2008 to 2017
$9.8M
Evasion of Antigen Presentation by Rhesus CytomegalovirusR01AI059457 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI FRUH, KLAUS J · 2005 to 2021
$6.2M
Viral Testing CoreU42OD010426 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI Andrew Haertel, Lauren Drew Martin · 2013 to 2026
$6.0M
Development and In Vivo Characterization of Safety-Enhanced RhCMV/SIV VectorsR01AI095113 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI PICKER, LOUIS J. · 2011 to 2015
$4.1M
Maternal immune protection against congenital CMV infectionDP2HD075699 · NICHD · DUKE UNIVERSITY · PI PERMAR, SALLIE R. · 2012 to 2017
$2.8M
HCRW_ HS-14-11Medical Research Council MR/L008734/1Medical Research Council MR/S00971X/1NIAID NIH HHS P01 AI094417NIAID NIH HHS P01 AI129859NIAID NIH HHS R01 AI059457NIAID NIH HHS R01 AI095113NIAID NIH HHS R01 AI175459NIAID NIH HHS R37 AI054292NIAID NIH HHS U19 AI128741NICHD NIH HHS DP2 HD075699NIH HHS P51 OD011092NIH HHS P51 OD011104NIH HHS P51 OD011107NIH HHS U42 OD010426NIH HHS U42 OD023038
6 · The paper itself

Abstract

Cytomegaloviruses (CMVs) are highly adapted to their host species resulting in strict species specificity. Hence, in vivo examination of all aspects of CMV biology employs animal models using host-specific CMVs. Infection of rhesus macaques (RM) with rhesus CMV (RhCMV) has been established as a representative model for infection of humans with HCMV due to the close evolutionary relationships of both host and virus. However, the only available RhCMV clone that permits genetic modifications is based on the 68-1 strain which has been passaged in fibroblasts for decades resulting in multiple genomic changes due to tissue culture adaptations. As a result, 68-1 displays reduced viremia in RhCMV-naïve animals and limited shedding compared to non-clonal, low passage isolates. To overcome this limitation, we used sequence information from primary RhCMV isolates to construct a full-length (FL) RhCMV by repairing all mutations affecting open reading frames (ORFs) in the 68-1 bacterial artificial chromosome (BAC). Inoculation of adult, immunocompetent, RhCMV-naïve RM with the reconstituted virus resulted in significant viremia in the blood similar to primary isolates of RhCMV and furthermore led to high viral genome copy numbers in many tissues at day 14 post infection. In contrast, viral dissemination was greatly reduced upon deletion of genes also lacking in 68-1. Transcriptome analysis of infected tissues further revealed that chemokine-like genes deleted in 68-1 are among the most highly expressed viral transcripts both in vitro and in vivo consistent with an important immunomodulatory function of the respective proteins. We conclude that FL-RhCMV displays in vitro and in vivo characteristics of a wildtype virus while being amenable to genetic modifications through BAC recombineering techniques.

Indexed as

ViremiaAnimalsCell LineChromosomes, Artificial, BacterialCytomegalovirusCytomegalovirus InfectionsDisease Models, AnimalDNA, RecombinantFemaleFibroblastsGenome, ViralHumansMacaca mulattaMaleMutationOpen Reading FramesDNA, Recombinant

Identifiers

PMID33232376
PMCPMC7723282
OpenAlexW3109432513

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.