Evidence map›Paper›PMID 24691437›Full record

ArticleThe Journal of clinical investigation2014

Cytomegalovirus pp65 limits dissemination but is dispensable for persistence.

Daniel Malouli, Scott G Hansen, Ernesto S Nakayasu, Emily E Marshall, Colette M Hughes, Abigail B Ventura, Roxanne M Gilbride, Matthew S Lewis, Guangwu Xu, Craig Kreklywich and 13 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 2 pooled it
2.8field-weighted citation impact, top 10% 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

30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.

  1. Pooled it
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  14. Cytomegaloviral determinants of CD8Science immunology · 2021
    Article
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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

23 authors at 3 institutions in 1 country.

Daniel Malouli
Scott G Hansen
Ernesto S Nakayasu
Emily E Marshall
Colette M Hughes
Abigail B Ventura
Roxanne M Gilbride
Matthew S Lewis
Guangwu Xu
Craig Kreklywich
Nathan Whizin
Miranda Fischer
Alfred W Legasse
Kasinath Viswanathan
Don Siess
David G Camp
Michael K Axthelm
Christoph Kahl
Victor R DeFilippis
Richard D Smith
Daniel N Streblow
Louis J Picker
Klaus Früh
Oregon Health & Science University · USPacific Northwest National Laboratory · USOregon National Primate Research Center · 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
WORKSHOP AND TRAINING ACTIVITIESP41RR018522 · NCRR · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI SMITH, RICHARD D · 2003 to 2011
$25.1M
Equipment Supplement Request for a Research Resource for Ultra-sensitive High Throughput ProteomicsP41GM103493 · NIGMS · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI SMITH, RICHARD D · 2012 to 2022
$22.6M
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 Gregory A Dissen · 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
Establishment of Specific Free Rhesus and Pigtail Macques ColoniesU24OD010850 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI AXTHELM, MICHAEL K · 2012 to 2015
$2.7M
Modulation of Innate Immune Responses by CytomegalovirusR01AI070890 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI FRUH, KLAUS J · 2008 to 2012
$2.4M
Inflammation and T Lymphocyte ImmunoregulationT32AI078903 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI HILL, ANN B · 2009 to 2013
$1.5M
NCRR NIH HHS 5P41RR018522-10NCRR NIH HHS P41 RR018522NIAID NIH HHS R01 AI059457NIAID NIH HHS R01 AI070890NIAID NIH HHS R01 AI070890-03S1NIAID NIH HHS R01 AI095113NIAID NIH HHS R01 AI095113-02NIAID NIH HHS T32 AI078903NIGMS NIH HHS 8 P41 GM103493-10NIGMS NIH HHS P41 GM103493NIH HHS P51 OD011092NIH HHS P51OD011092NIH HHS U24 OD010850NIH HHS U42 OD010426
6 · The paper itself

Abstract

The most abundantly produced virion protein in human cytomegalovirus (HCMV) is the immunodominant phosphoprotein 65 (pp65), which is frequently included in CMV vaccines. Although it is nonessential for in vitro CMV growth, pp65 displays immunomodulatory functions that support a potential role in primary and/or persistent infection. To determine the contribution of pp65 to CMV infection and immunity, we generated a rhesus CMV lacking both pp65 orthologs (RhCMVΔpp65ab). While deletion of pp65ab slightly reduced growth in vitro and increased defective particle formation, the protein composition of secreted virions was largely unchanged. Interestingly, pp65 was not required for primary and persistent infection in animals. Immune responses induced by RhCMVΔpp65ab did not prevent reinfection with rhesus CMV; however, reinfection with RhCMVΔUS2-11, which lacks viral-encoded MHC-I antigen presentation inhibitors, was prevented. Unexpectedly, induction of pp65b-specific T cells alone did not protect against RhCMVΔUS2-11 challenge, suggesting that T cells targeting multiple CMV antigens are required for protection. However, pp65-specific immunity was crucial for controlling viral dissemination during primary infection, as indicated by the marked increase of RhCMVΔpp65ab genome copies in CMV-naive, but not CMV-immune, animals. Our data provide rationale for inclusion of pp65 into CMV vaccines but also demonstrate that pp65-induced T cell responses alone do not recapitulate the protective effect of natural infection.

Indexed as

AnimalsAntigen PresentationCell LineCytomegalovirusCytomegalovirus InfectionsCytomegalovirus VaccinesGene DeletionHumansMacaca mulattaMicePhosphoproteinsT-LymphocytesViral Matrix Proteinscytomegalovirus matrix protein 65kDaCytomegalovirus VaccinesPhosphoproteinsViral Matrix Proteins

Identifiers

PMID24691437
PMCPMC4002596
OpenAlexW2006586087

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.