Eun-Seok Choi

Respiratory viral infections impose a substantial global health burden. Among these, respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in young children, immunocompromised individuals, and older adults. During the COVID-19 pandemic, co-circulation of RSV and COVID-19 led to increasing reports of coinfections, which continue to occur in endemic settings. In this study, we employed a physiologically relevant in vitro model comprising human primary respiratory epithelial cells cultured at an air–liquid interface (ALI), together with the A549-ACE2 cell line model, to investigate the impacts of sequential RSV and SARS-CoV-2 infection. This platform enabled us to examine how host responses primed by an initial RSV infection influence subsequent SARS-CoV-2 infection. Our findings demonstrate that RSV-induced host response significantly restricted SARS-CoV-2 gene expression. Notably, we identified that RSV induced phospholipid scramblase 1 (PLSCR1), an interferon-stimulated gene previously implicated in antiviral defense against SARS-CoV-2, as a novel potential mediator of this effect. Together, these mechanisms are consistent with the phenomenon of viral interference, whereby one respiratory virus transiently reduces susceptibility to another, providing a biologically plausible explanation for cross-protective effects observed in sequential infections.

Herpes simplex virus type 1 (HSV-1) is a continuous health challenge, and current antiviral treatments cannot cure the virus. As life expectancy continues to increase worldwide, HSV-1 should remain a focus to minimize its associated health complications within the aging population. While often asymptomatic, HSV-1 causes oral and cutaneous lesions and establishes latency with periodic reactivation. Antivirals reduce symptoms but do not eradicate the virus. Emerging evidence links HSV-1 to Alzheimer’s disease (AD) via chronic neuroinflammation, amyloid-beta and tau accumulation, oxidative stress, and synaptic dysfunction, with viral proteins detected in AD-affected brain regions. This review assesses the current evidence for HSV-1 in dementia pathogenesis, examines antiviral strategies as potential neuroprotective interventions, and outlines the experimental models required to establish causality.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants, young children, and immunocompromised individuals. Currently, FDA-approved monoclonal antibody therapies are limited to infants and young children with severe RSV disease. As a result, there is an urgent need for comprehensive studies of RSV pathogenesis to support the development of new therapeutic strategies. Exchange proteins directly activated by cAMP (EPAC) have recently emerged as key regulators in various viral infections. Our previous work identified EPAC isoform 2 (EPAC2) as a critical factor in RSV replication and host innate immune responses. However, the molecular mechanisms underlying EPAC2’s role in RSV infection remain unclear. In this study, we investigated EPAC2-mediated RSV infection by identifying EPAC2-interacting proteins. Proteomics and immunoprecipitation analyses revealed that junction plakoglobin (JUP) interacts with EPAC2 in both mock- and RSV-infected cells, with this interaction notably enhanced during RSV infection. To determine JUP’s role in RSV infection, we compared viral replication in JUP-deficient and control cells. JUP downregulation significantly reduced the production of infectious RSV particles, likely by impairing viral budding and viral gene transcription. Moreover, our findings indicate that JUP is essential for an effective cellular immune response to RSV infection. Together, these results suggest that EPAC2 and JUP may cooperatively regulate RSV replication and dissemination.

Chronic obstructive pulmonary disease (COPD) and lung cancer represent formidable challenges in global health, characterized by intricate pathophysiological mechanisms and multifaceted disease progression. This comprehensive review integrates insights from diverse perspectives to elucidate the intricate roles of long non-coding RNAs (lncRNAs) in the pathogenesis of COPD and lung cancer, focusing on their diagnostic, prognostic, and therapeutic implications. In the context of COPD, dysregulated lncRNAs, such as NEAT1, TUG1, MALAT1, HOTAIR, and GAS5, emerge as pivotal regulators of genes involved in the disease pathogenesis and progression. Their identification, profiling, and correlation with the disease severity present promising avenues for prognostic and diagnostic applications, thereby shaping personalized disease interventions. These lncRNAs are also implicated in lung cancer, underscoring their multifaceted roles and therapeutic potential across both diseases. In the domain of lung cancer, lncRNAs play intricate modulatory roles in disease progression, offering avenues for innovative therapeutic approaches and prognostic indicators. LncRNA-mediated immune responses have been shown to drive lung cancer progression by modulating the tumor microenvironment, influencing immune cell infiltration, and altering cytokine production. Their dysregulation significantly contributes to tumor growth, metastasis, and chemo-resistance, thereby emphasizing their significance as therapeutic targets and prognostic markers. This review summarizes the transformative potential of lncRNA-based diagnostics and therapeutics for COPD and lung cancer, offering valuable insights into future research directions for clinical translation and therapeutic development.

Keywords: Chronic Obstructive Pulmonary Disease (COPD), Long Non-Coding RNAs (lncRNAs), Molecular Pathogenesis, Inflammation, Lung Cancer, Diagnostic Biomarkers

We have previously reported that FAM188B showed significant differential exon usage in cancers (NCBI GEO GSE30727), but the expression and function of FAM188B is not well characterized. In the present study, we explored the functions of FAM188B by a knockdown strategy, using siRNAs specific for FAM188B in colon cancer cell lines. FAM188B is a novel gene that encodes a protein that is evolutionarily conserved among mammals. Its mRNA has been found to be highly expressed in most solid tumors, including colorectal cancer. FAM188B knockdown induced cell growth inhibition due to an increase in apoptosis in colon cancer cell lines. Interestingly, siFAM188B treatment induced the upregulation and activation of p53, and consequently increased p53-regulated pro-apoptotic proteins, PUMA and BAX. Proteomic analysis of FAM188B immunocomplexes revealed p53 and USP7 as putative FAM188B-interacting proteins. Deletion of the putative USP7-binding motif in FAM188B reduced complex formation of FAM188B with USP7. It is noteworthy that FAM188B knockdown resulted in a decrease in overall ubiquitination in the p53 immunocomplexes, as well as p53 ubiquitination, because USP7 is involved in p53 deubiquitination. FAM188B knockdown inhibited both colony formation and anchorage-independent growth in vitro. In addition, FAM188B knockdown by siRNA reduced tumor growth in xenografted mice, with an increase in p53 proteins. Taken together, our data suggest that FAM188B is a putative oncogene that functions via interaction with USP7. Therefore, control of FAM188B could be a possible target to inhibit tumor growth.

Kim YK, et al. Ann Rehabil Med. 2018 Apr;42(2):260-269. https://doi.org/10.5535/arm.2018.42.2.260