What is the clinical evidence from this study?

Study design: Other. Population: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from patients with dilated cardiomyopathy carrying DES mutations (DESS46Y, DESD214-E245del, DESP419H) compared to hiPSC-CMs from healthy donors (n=3). Intervention: Coxsackievirus B3/28 (CVB3/28) infection vs. uninfected cardiomyocytes. Primary outcome: Cardiomyocyte structural integrity disruption and contractile function impairment post CVB3/28 infection.

What does this research mean for the field?

DES mutations in cardiomyocytes increase susceptibility to coxsackievirus B3 infection by enhancing viral replication, impairing the IFN-β antiviral response, and exacerbating contractile dysfunction. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

What question did this study set out to answer?

The study investigates how desmin mutations affect the susceptibility of cardiomyocytes to coxsackievirus B3 infection and the underlying mechanisms.

March 1, 2026Open Access

Desmin mutations in cardiomyocytes increase susceptibility to coxsackievirus B3 infection by impairing antiviral IFN-β response and upregulating viral receptors expression

Key Result

DES mutations (DESS46Y, DESD214-E245del, DESP419H) in cardiomyocytes increased CVB3/28 viral replication by 1.5- to 3-fold and impaired IFN-β antiviral response, exacerbating contractile dysfunction compared to control cells.

Key Points

The study investigates how desmin mutations affect the susceptibility of cardiomyocytes to coxsackievirus B3 infection and the underlying mechanisms.
Isolation of human induced pluripotent stem cell-derived cardiomyocytes from healthy and mutated donors
Infection of cardiomyocytes with coxsackievirus B3/28
Assessment of viral replication, protein expression, and contractile function through various analyses
Quantification of viral receptors and immunofluorescence imaging to assess structural integrity.
Mutated cardiomyocytes showed increased viral replication and reduced contractile function post-infection
Infection led to lower IFN-β response and increased expression of viral receptors in DESmut-CMs
CVB3/28 infection caused more significant structural damage in cells with desmin mutations than in control cells.

Structured PICO

Does Coxsackievirus B3/28 infection exacerbate structural and functional impairment in cardiomyocytes carrying DES mutations compared to healthy controls?

Population

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a healthy donor (control-CMs) and from 3 patients carrying DES mutations (DESS46Y, DESD214-E245del, or DESP419H).

Intervention

Infection with cardiovirulent enterovirus Coxsackievirus B3/28 (CVB3/28) at a multiplicity of infection (MOI) of 1.

Comparator

Uninfected hiPSC-CMs (baseline) and infected control-CMs (from healthy donor).

Outcome

Structural changes (sarcomeric organization, desmin network) and contractile function (spontaneous beating activity, contraction kinetics) at 24 hours post-infection.surrogate

DES mutations synergize with CVB3/28 infection to impair cardiomyocyte structure and contractility by enhancing viral replication and blunting antiviral IFN-β responses.

Limitations

Study conducted in vitro using hiPSC-derived cardiomyocytes which may not fully represent in vivo cardiac environment
Small number of cell lines studied limiting generalizability
Lack of clinical outcome data linking infection findings to patient prognosis
No randomization or blinding due to study design
Structural and functional assessments limited to 24 hours post-infection
Potential variability in mutation-specific effects not fully explored across larger cohorts

Abstract

Desmin-related cardiomyopathies caused by mutations in the DES gene are characterized by cytoskeletal disorganization and impaired cardiomyocyte function. Viral infections, particularly with Coxsackievirus B3 (CVB3), have been implicated as environmental triggers for cardiac decompensation. However, the interaction between desmin mutations and viral infection has never been explored. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a healthy donor (control-CMs) and from patients carrying DESS46Y, DESD214−E245del, or DESP419H mutations (DESmut-CMs) were infected with the cardiovirulent enterovirus CVB3/28. Structural changes were assessed by immunofluorescence for sarcomeric proteins and desmin. Contractile function was evaluated through video-based motion tracking. Viral replication, protein expression and antiviral responses were measured via plaque assays, immunostaining, and qPCR. Coxsackievirus and Adenovirus Receptor (CAR) and cell-surface vimentin expression were quantified post-infection. DESmut-CMs exhibited baseline sarcomeric disorganization and desmin aggregation, which were further aggravated by CVB3/28 infection in a mutation-specific manner. CVB3/28 significantly reduced spontaneous contractility in control-CMs, DESS46Y, and DESP419H-CMs, with minimal effect in DESD214−E245del-CMs. Infected DESmut-CMs showed enhanced viral replication, increased VP1 expression and elevated virion release. This was accompanied by a stunted IFN-β response, reduced APOBEC3A expression, and infection-induced upregulation of viral receptors CAR and cell-surface vimentin. CVB3/28 infection compromises the structural integrity and contractile function of cardiomyocytes and exerts a more severe effect in cells harboring DES mutations. These findings underscore a pathogenic synergy between genetic cytoskeletal defects and viral infection, revealing a mechanistic basis for the heightened vulnerability of patients carrying mutation in DES gene to virus-induced cardiac decompensation. CVB3/28 infection disrupts cardiomyocyte structure and impairs contractility, with more severe effects in cells carrying DES mutations. By enhancing viral replication and weakening antiviral defenses, DES mutations act synergistically with CVB3/28 infection to increase the risk of cardiac dysfunction.

Bookmark

View Full Paper