Ultrastructural and Functional Characterization of Mitochondrial Dynamics Induced by Human Respiratory Syncytial Virus Infection in HEp-2 Cells

Abstract

Human respiratory syncytial virus (hRSV) is the leading cause of acute lower respiratory tract infections in children under five years of age and older adults worldwide. During hRSV infection, host cells undergo changes in endomembrane organelles, including mitochondria. This organelle is responsible for energy production in the cell and plays an important role in the antiviral response. The present study focuses on characterizing the ultrastructural and functional changes during hRSV infection using thin-section transmission electron microscopy and RT-qPCR. Here we report that hRSV infection alters mitochondrial morphodynamics by regulating the expression of key genes in the antiviral response process, such as Mfn1, VDAC2, and PINK1. Our results suggest that hRSV alters mitochondrial morphology during infection, producing a mitochondrial phenotype with shortened cristae, swollen matrix, and damaged membrane. We also observed that hRSV infection modulates the expression of the aforementioned genes, possibly as an evasion mechanism in the face of cellular antiviral response. Taken together, these results advance our knowledge of the ultrastructural alterations associated with hRSV infection and might guide future therapeutic efforts to develop effective antiviral drugs for hRSV treatment.

Ciliary Function, Antigen Stasis and Asthma

“…RSV infects the respiratory epithelium, leading to chronic inflammation [44], and induces loss of cilia activity, two factors that determine mucus clearance and the increase in sputum volume. Other changes caused by RSV includes ultrastructural abnormalities con-fined to ciliated cells, such as increased cilia loss and mitochondrial damage [44,45]. I hypothesize that secondary ciliary dysmotility caused by viral infections like RSV could, as in PCD, cause antigen stasis, contributing to an asthma diathesis46.…”

Enterovirus 71 leads to abnormal mitochondrial dynamics in human neuroblastoma SK-N-SH cells

“…The interplay of these processes bestows mitochondria with numerous advantages, including efficient transport, enhanced homogenization of the mitochondrial population, and effective oxidative phosphorylation ( Chan, 2020 ). An increasing body of research underscores the role of mitochondrial dysfunction, particularly in mitochondrial dynamics, as a pivotal player in the pathogenesis of viral diseases ( Choi et al., 2023 ; Khan et al., 2015 ; Lara-Hernandez et al., 2023 ).…”