Evidence map›Paper›PMID 39655954›Full record

ArticleJournal of virology2025

Third intracellular loop of HCMV US28 is necessary for signaling and viral reactivation.

Samuel Medica, Michael Denton, Nicole L Diggins, Olivia Kramer-Hansen, Lindsey B Crawford, Adam T Mayo, Wilma D Perez, Michael A Daily, Christopher J Parkins, Luke E Slind and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of virology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
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

21 authors.

Samuel MedicaVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.ORCID 0000-0002-3611-3715
Michael DentonVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
Nicole L DigginsVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.ORCID 0000-0001-8007-7865
Olivia Kramer-HansenDepartment of Biomedical Sciences Molecular Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Lindsey B CrawfordVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.ORCID 0000-0003-1248-253X
Adam T MayoVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
Wilma D PerezVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
Michael A DailyVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
Christopher J ParkinsVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
Luke E SlindVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
Lydia J PungVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
Whitney C WeberVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
Hannah K JaegerVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
Zachary J StreblowVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
Gauthami SulgeyVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
Craig N KreklywichVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
Timothy AlexanderVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
Mette M RosenkildeDepartment of Biomedical Sciences Molecular Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Patrizia CaposioVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.ORCID 0000-0001-7579-849X
Meaghan H HancockVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.ORCID 0000-0003-2945-0147
Daniel N StreblowVaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.ORCID 0000-0002-6828-2492

Funding

The Administrative CoreP01AI127335 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI Patrizia Caposio · 2017 to 2026
$24.6M
MOLECULAR ASPECTS OF CYTOMEGALOVIRUS LATENCYR01AI021640 · NIAID · UNIVERSITY OF GUELPH · PI Meaghan H Hancock · 1985 to 2026
$8.1M
Molecular Aspects of Cytomegalovirus LatencyR37AI021640 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI HANCOCK, MEAGHAN H · 2018 to 2024
$4.0M
Interdisciplinary Training in Microbial Pathogenesis and ImmunologyT32AI170496 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI Patrizia Caposio, Scott M Landfear · 2023 to 2026
$1.5M
HHS | National Institutes of Health (NIH) AI127335HHS | National Institutes of Health (NIH) AI170496-01A1HHS | National Institutes of Health (NIH) AI21640NIAID NIH HHS P01 AI127335NIAID NIH HHS R01 AI021640NIAID NIH HHS R37 AI021640NIAID NIH HHS T32 AI170496
6 · The paper itself

Abstract

The human cytomegalovirus (HCMV) encoded chemokine receptor US28 plays a critical role in viral pathogenesis, mediating several processes such as cellular migration, differentiation, transformation, and viral latency and reactivation. Despite significant research examining the signal transduction pathways utilized by US28, the precise mechanism by which US28 activates these pathways remains unclear. We performed a mutational analysis of US28 to identify signaling domains that are critical for functional activities. Our results indicate that specific residues within the third intracellular loop (ICL3) of US28 are major determinants of G-protein coupling and downstream signaling activity. Alanine substitutions at positions S218, K223, and R225 attenuated US28-mediated activation of MAPK and RhoA signal transduction pathways. Furthermore, we show that mutations at positions S218, K223, or R225 result in impaired coupling to multiple Gα isoforms. However, these substitutions did not affect US28 plasma membrane localization or the receptor internalization rate. Utilizing CD34

Indexed as

CytomegalovirusCytomegalovirus InfectionsReceptors, ChemokineSignal TransductionViral ProteinsVirus ActivationAnimalsHumansMiceMutationVirus LatencyReceptors, ChemokineUS28 receptor, CytomegalovirusViral ProteinscytomegalovirusG-protein-coupled receptorlatencyreactivationsignal transduction

Identifiers

PMID39655954
PMCPMC11784217

What OpenQuestion holds

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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 OpenQuestion graph.