Evidence map›Paper›PMID 42655695›Full record

ArticleViruses2026

Metabolomic Analysis of Lytic KSHV Infection: Induced Host Nucleotide Metabolism Is Required for Infectious Virus Production.

Fatima Hisam, Emma A Winn, Spandan Mukherjee, Savannah E Price, Yennifer A Gaspar, Claire Wang, Hamid R Baniasadi, Tracie Delgado, Erica L Sanchez

Abstract read
In one paragraph

Article in Viruses, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Fatima HisamDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.ORCID 0009-0002-3735-8113
Emma A WinnDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.ORCID 0009-0000-4290-8461
Spandan MukherjeeDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.ORCID 0009-0005-6707-990X
Savannah E PriceDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.ORCID 0009-0009-7254-422X
Yennifer A GasparDepartment of Biology, Seattle Pacific University, Seattle, WA 98119, USA.
Claire WangDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.ORCID 0009-0003-7673-8490
Hamid R BaniasadiDepartment of Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Tracie DelgadoDepartment of Biology, Seattle Pacific University, Seattle, WA 98119, USA.ORCID 0000-0001-8070-657X
Erica L SanchezDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.ORCID 0000-0002-9079-1090

Funding

Molecular Mechanisms Drive Metabolic and Lipid Profiles that Define Cells in the Latent and Lytic Stages of Viral InfectionR35GM160182 · NIGMS · UNIVERSITY OF TEXAS DALLAS · PI Erica Lee Sanchez · 2025 to 2026
$866k
The Identification of Clinically Relevant Metabolic Inhibitors to Treat Gammaherpesvirus InfectionsR15AI185858 · NIAID · SEATTLE PACIFIC UNIVERSITY · PI DELGADO, TRACIE · 2024 to 2024
$405k
NIAID NIH HHS R15 AI185858NIGMS NIH HHS 1R35GM160182NIGMS NIH HHS R35 GM160182NIH HHS 1R15AI185858-02
6 · The paper itself

Abstract

Kaposi's Sarcoma Herpesvirus (KSHV) is the etiological agent of Kaposi's Sarcoma (KS), which induces metabolic stress in infected host cells. KSHV reprograms host metabolic pathways for efficient viral replication and infectious virion production. Here, we report a time-course global metabolomics study conducted in iSLK.BAC16 cells to compare latent and lytic KSHV infection. Our data show that amino acid, central carbon, and nucleotide metabolic pathways are highly dysregulated upon reactivation. During lytic KSHV infection, pathway enrichment analysis identifies purine and pyrimidine metabolism as the top two most significantly impacted and dysregulated pathways. Further experiments have shown that nucleotide metabolism is required during lytic KSHV infection to produce maximal infectious virus. Treatment with the FDA-approved drug, methotrexate (MTX), a folate antagonist that decreases nucleotide metabolism by reducing tetrahydrofolate cofactors, significantly reduced KSHV copy number and late lytic viral gene expression upon reactivation compared to controls. Additionally, titers of cell-free supernatants from MTX-treated lytic samples showed a significant reduction in infectious virion production. Furthermore, MTX significantly decreased the viral titer of murine herpesvirus 68 (MHV-68), a model virus to study gammaherpesvirus. Overall, our study demonstrates that metabolic inhibition during lytic gammaherpesvirus infection decreases productive infection and hence serves as a potential therapeutic antiviral target.

Indexed as

Herpesvirus 8, HumanMetabolomicsNucleotidesVirus ReplicationAnimalsCell LineHost-Pathogen InteractionsHumansMetabolic Networks and PathwaysMethotrexateRhadinovirusSarcoma, KaposiVirionVirus ActivationMethotrexateNucleotidesKaposi’s Sarcoma Herpesvirus (KSHV)Kaposi’s Sarcoma (KS)lytic replicationmetabolomicsmethotrexate (MTX)nucleotide metabolism

Identifiers

PMID42655695
PMCPMC13517163

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.