Evidence map›Paper›PMID 28459883›Full record

ArticlePLoS pathogens2017

NLRX1 negatively modulates type I IFN to facilitate KSHV reactivation from latency.

Zhe Ma, Sharon E Hopcraft, Fan Yang, Alex Petrucelli, Haitao Guo, Jenny P-Y Ting, Dirk P Dittmer, Blossom Damania

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.2field-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

28 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Focusing on the Cell Type Specific Regulatory Actions of NLRX1.International journal of molecular sciences · 2021
    Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Behind the Scenes: Nod-Like Receptor X1 Controls Inflammation and Metabolism.Frontiers in cellular and infection microbiology · 2020
    Review
  17. Article
  18. Article
  19. Article
  20. Pathogenesis of Human Gammaherpesviruses: Recent Advances.Current clinical microbiology reports · 2019
    Article
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

8 authors at 1 institution in 1 country.

Zhe MaLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.ORCID http://orcid.org/0000-0002-7222-2556
Sharon E HopcraftLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.ORCID http://orcid.org/0000-0002-2564-3913
Fan YangLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Alex PetrucelliLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Haitao GuoLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Jenny P-Y TingLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.ORCID http://orcid.org/0000-0002-7846-0395
Dirk P DittmerLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.ORCID http://orcid.org/0000-0003-4968-5656
Blossom DamaniaLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, United States of America.ORCID http://orcid.org/0000-0002-9205-1774
University of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Vironomics and Biostatistics CoreP01CA019014 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BLOSSOM A DAMANIA, NANCY JOAN RAAB-TRAUB · 1985 to 2026
$43.8M
Integrated Training in Cancer Model SystemsT32CA009156 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J. · 1985 to 2020
$19.7M
Proteomics Pathway DiscoveryU19AI109965 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DUNCAN, JOSEPH A · 2014 to 2018
$14.9M
ART Modulation of Viral Pathogenesis in Oral EpitheliaR01DE018304 · NIDCR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DITTMER, DIRK P · 2007 to 2025
$6.9M
Modulation of Innate Immunity by KSHVR01DE028211 · NIDCR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAMANIA, BLOSSOM A · 2018 to 2022
$2.1M
NCI NIH HHS P01 CA019014NCI NIH HHS P30 CA016086NCI NIH HHS T32 CA009156NIAID NIH HHS U19 AI109965NIDCR NIH HHS R01 DE018304NIDCR NIH HHS R01 DE028211
6 · The paper itself

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is a herpesvirus that is linked to Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). KSHV establishes persistent latent infection in the human host. KSHV undergoes periods of spontaneous reactivation where it can enter the lytic replication phase of its lifecycle. During KSHV reactivation, host innate immune responses are activated to restrict viral replication. Here, we report that NLRX1, a negative regulator of the type I interferon response, is important for optimal KSHV reactivation from latency. Depletion of NLRX1 in either iSLK.219 or BCBL-1 cells significantly suppressed global viral transcription levels compared to the control group. Concomitantly, fewer viral particles were present in either cells or supernatant from NLRX1 depleted cells. Further analysis revealed that upon NLRX1 depletion, higher IFNβ transcription levels were observed, which was also associated with a transcriptional upregulation of JAK/STAT pathway related genes in both cell lines. To investigate whether IFNβ contributes to NLRX1's role in KSHV reactivation, we treated control and NLRX1 depleted cells with a TBK1 inhibitor (BX795) or TBK1 siRNA to block IFNβ production. Upon BX795 or TBK1 siRNA treatment, NLRX1 depletion exhibited less inhibitory effects on reactivation and infectious virion production, suggesting that NLRX1 facilitates KSHV lytic replication by negatively regulating IFNβ responses. Our data suggests that NLRX1 plays a positive role in KSHV lytic replication by suppressing the IFNβ response during the process of KSHV reactivation, which might serve as a potential target for restricting KSHV replication and transmission.

Indexed as

DNA ReplicationVirus ActivationCastleman DiseaseCell LineGene Expression RegulationHerpesvirus 8, HumanHumansInterferon Type ILymphoma, Primary EffusionMitochondrial ProteinsSarcoma, KaposiVirus LatencyInterferon Type IMitochondrial ProteinsNLRX1 protein, human

Identifiers

PMID28459883
PMCPMC5426799
OpenAlexW2610588291

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.