Evidence map›Paper›PMID 36418547›Full record

ArticleCell death and differentiation2023

Caspase-8 is required for HSV-1-induced apoptosis and promotes effective viral particle release via autophagy inhibition.

Francesca Marino-Merlo, Anusha Klett, Emanuela Papaianni, Selene Francesca Anna Drago, Beatrice Macchi, María Gabriela Rincón, Federica Andreola, Annalucia Serafino, Sandro Grelli, Antonio Mastino and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

23 citing papers in PubMed, 29 citations in OpenAlex.

  1. Cell death network regulation in HSV infection: immune evasion versus host defense.Apoptosis : an international journal on programmed cell death · 2026
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  5. Journal of agricultural and food chemistry · 2026
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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

11 authors at 4 institutions in 2 countries.

Francesca Marino-Merlo *Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98166, Messina, Italy.
Anusha Klett *Institute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, 79104, Freiburg, Germany.
Emanuela Papaianni *Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98166, Messina, Italy.
Selene Francesca Anna DragoDepartment of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98166, Messina, Italy.
Beatrice MacchiDepartment of Chemical Science and Technology, University of Rome "Tor Vergata", 00133, Rome, Italy.
María Gabriela RincónInstitute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, 79104, Freiburg, Germany.
Federica AndreolaThe Institute of Translational Pharmacology, CNR, 00133, Rome, Italy.
Annalucia SerafinoThe Institute of Translational Pharmacology, CNR, 00133, Rome, Italy.ORCID http://orcid.org/0000-0002-1142-4752
Sandro GrelliDepartment of Experimental Medicine, University of Rome "Tor Vergata", 00133, Rome, Italy. grelli@med.uniroma2.it.ORCID http://orcid.org/0000-0003-1028-3203
Antonio Mastino *The Institute of Translational Pharmacology, CNR, 00133, Rome, Italy.ORCID http://orcid.org/0000-0002-0338-6450
Christoph Borner *Institute of Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, 79104, Freiburg, Germany. christoph.borner@uniklinik-freiburg.de.ORCID http://orcid.org/0000-0001-5127-7630
Istituto di Farmacologia Traslazionale · ITUniversity of Freiburg · DEUniversity of Messina · ITUniversity of Rome Tor Vergata · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Regulated cell death (RCD) plays an important role in the progression of viral replication and particle release in cells infected by herpes simplex virus-1 (HSV-1). However, the kind of RCD (apoptosis, necroptosis, others) and the resulting cytopathic effect of HSV-1 depends on the cell type and the species. In this study, we further investigated the molecular mechanisms of apoptosis induced by HSV-1. Although a role of caspase-8 has previously been suggested, we now clearly show that caspase-8 is required for HSV-1-induced apoptosis in a FADD-/death receptor-independent manner in both mouse embryo fibroblasts (MEF) and human monocytes (U937). While wild-type (wt) MEFs and U937 cells exhibited increased caspase-8 and caspase-3 activation and apoptosis after HSV-1 infection, respective caspase-8-deficient (caspase-8-/-) cells were largely impeded in any of these effects. Unexpectedly, caspase-8-/- MEF and U937 cells also showed less virus particle release associated with increased autophagy as evidenced by higher Beclin-1 and lower p62/SQSTM1 levels and increased LC3-I to LC3-II conversion. Confocal and electron microscopy revealed that HSV-1 stimulated a strong perinuclear multivesicular body response, resembling increased autophagy in caspase-8-/- cells, entrapping virions in cellular endosomes. Pharmacological inhibition of autophagy by wortmannin restored the ability of caspase-8-/- cells to release viral particles in similar amounts as in wt cells. Altogether our results support a non-canonical role of caspase-8 in both HSV-1-induced apoptosis and viral particle release through autophagic regulation.

Indexed as

Herpesvirus 1, HumanAnimalsApoptosisAutophagyCaspase 3Caspase 8HumansMiceVirionCaspase 3Caspase 8

Identifiers

PMID36418547
PMCPMC10070401
OpenAlexW4309896792

What OpenQuestion 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 OpenQuestion graph.