Background: Myocarditis is inflammation of the heart muscle that can follow various viral infections. Why children only rarely develop life-threatening acute viral myocarditis (AVM), given that the causal viral infections are common, is unknown. Genetic lesions might underlie such susceptibilities. Mouse genetic studies demonstrated that interferon (IFN)-α/β immunity defects increased susceptibility to virus-induced myocarditis. Moreover, variations in human TLR3, a potent inducer of IFNs, were proposed to underlie AVM.
Objectives: This study sought to evaluate the hypothesis that human genetic factors may underlie AVM in previously healthy children.
Methods: We tested the role of TLR3-IFN immunity using human induced pluripotent stem cell-derived cardiomyocytes. We then performed whole-exome sequencing of 42 unrelated children with acute myocarditis (AM), some with proven viral causes.
Results: We found that TLR3- and STAT1-deficient cardiomyocytes were not more susceptible to Coxsackie virus B3 (CVB3) infection than control cells. Moreover, CVB3 did not induce IFN-α/β and IFN-α/β-stimulated genes in control cardiomyocytes. Finally, exogenous IFN-α did not substantially protect cardiomyocytes against CVB3. We did not observe a significant enrichment of rare variations in TLR3- or IFN-α/β-related genes. Surprisingly, we found that homozygous but not heterozygous rare variants in genes associated with inherited cardiomyopathies were significantly enriched in AM-AVM patients compared with healthy individuals (p = 2.22E-03) or patients with other diseases (p = 1.08E-04). Seven of 42 patients (16.7%) carried rare biallelic (homozygous or compound heterozygous) nonsynonymous or splice-site variations in 6 cardiomyopathy-associated genes (BAG3, DSP, PKP2, RYR2, SCN5A, or TNNI3).
Conclusions: Previously silent recessive defects of the myocardium may predispose to acute heart failure presenting as AM, notably after common viral infections in children.
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http://dx.doi.org/10.1016/j.jacc.2017.01.043 | DOI Listing |
Infect Drug Resist
January 2025
Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
Objective: To evaluate the diagnostic performance and clinical impact of targeted next-generation sequencing (tNGS) in patients with suspected lower respiratory tract infections.
Methods: Following propensity score matching, we compared the diagnostic performances of tNGS and metagenomic next-generation sequencing (mNGS). Furthermore, the diagnostic performance of tNGS was compared with that of culture, and its clinical impact was assessed.
ScientificWorldJournal
January 2025
Department of Microbiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.
Infection by human herpes simplex virus type 1 and type 2 (HSV-1/2) is common globally though with wide regional variability. Seroepidemiology of HSV-1/2 infections is of utmost importance in formulating control strategies, but there is a paucity of data from many regions of India. This study aimed to determine the prevalence of anti-HSV-1/2 antibodies in Uttarakhand and adjoining areas and to study its pattern and distribution in different subgroups.
View Article and Find Full Text PDFFront Vet Sci
January 2025
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China.
Aleutian mink disease (mink plasmacytosis) is a severe immune complex-mediated condition caused by the Aleutian Mink Disease Virus (AMDV), the most significant pathogen affecting mink health in the industry. Several studies have shown that AMDV epidemics can result in millions to tens of millions of dollars in economic losses worldwide each year. In this study, we developed a TaqMan probe-based real-time PCR technology (TaqMan-qPCR) for the specific, sensitive, and reproducible detection and quantification of AMDV in mink tissues by the VP2 gene, achieving detection limits as low as 1.
View Article and Find Full Text PDFInt Med Case Rep J
January 2025
Kilimanjaro Christian Medical University College of Tumaini University, Moshi, Tanzania.
Background: Neurocysticercosis (NCC) and Acquired Human Immunodeficiency Syndrome (AIDS) are both highly prevalent in Africa. Clinical presentation of NCC ranges from asymptomatic to manifestations, including epileptic seizures, severe progressive headache, and focal neurological deficits. It is influenced by the number, size, location, and stage of the cysts, as well as the parasite's potential to cause inflammation and the immunological response of the host.
View Article and Find Full Text PDFCureus
December 2024
Pediatric Intensive Care Unit, Pediatric Department, King Saud University Medical City, College of Medicine, King Saud University, Riyadh, SAU.
Para-pneumonic effusion in children is often associated with bacterial infections; however, dual viral infections, including respiratory syncytial virus (RSV) and COVID-19, can also lead to severe respiratory complications, as demonstrated in this case. This case report presents the clinical course of a pediatric patient with both RSV and COVID-19 infections, leading to para-pneumonic effusion. A three-year-old girl with a history of asthma and prior febrile convulsions presented to the Emergency Department with fever, cough, vomiting, and fatigue.
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