Un Yung Choi

Herpesviruses establish lifelong latency and can reactivate when antiviral immune surveillance is compromised. Since the onset of COVID-19 pandemic, reactivation of multiple human herpesviruses has increasingly been documented, particularly in patients with severe or critical illness. Herpesvirus reactivation has been associated with prolonged intensive care unit stays, secondary infections, greater ventilatory support requirements, and increased mortality. This review summarizes the latency and reactivation characteristics of the major human herpesviruses and evaluates the clinical evidence linking their reactivation to SARS-CoV-2 infection. We further propose a multifactorial mechanistic framework involving impaired T-cell and natural killer cell surveillance, defective interferon-mediated immunity, sustained inflammation and cytokine signaling, direct and indirect effects of SARS-CoV-2 proteins, and host transcriptional and epigenetic reprogramming. However, despite accumulating clinical and experimental evidence supporting a biologically plausible association between SARS-CoV-2 infection and herpesvirus reactivation, the precise mechanisms underlying this interplay remain incompletely understood. Longitudinal viral monitoring, physiologically relevant latency models, and mechanistic intervention studies are therefore needed to establish causality and identify patients who may benefit from targeted surveillance or antiviral treatment.

Background/Objectives: Tranexamic acid (TXA) reduces mortality in patients with massive hemorrhage by inhibiting fibrinolysis. However, it is associated with an increased risk of thrombosis. The activation of neutrophil extracellular traps (NETs) has been implicated in the formation of thrombosis. This study investigated the effects of tranexamic acid on circulating and localized NETs, neutrophils, platelets, and the vascular endothelium in a mouse model of thrombosis. Methods: A ferric chloride-induced thrombosis mouse model was used and divided into five groups: a Control group that received intraperitoneal phosphate-buffered saline (PBS), and four experimental groups that received intraperitoneal tranexamic acid at doses of 5 mg/kg, 10 mg/kg, 20 mg/kg, and 30 mg/kg, respectively. To evaluate the expression of circulating and localized NETs, neutrophils, platelets, vascular endothelial cells, fibrinogen, and D-dimer, the following markers were analyzed: myeloperoxidase (MPO), neutrophil marker, cluster of differentiation (CD)31, CD34, fibrinogen α-chain, and D-dimer. These markers were assessed using flow cytometry, immunohistofluorescence staining, and Western blot analysis. The primary endpoint was the differential expression of anti-MPO antibody among the groups. Results: In total, data from 20 thrombosis mouse models were analyzed. For each group, four samples were assessed by flow cytometry, and three samples by immunohistofluorescence staining and Western blot analysis, respectively. In the flow cytometric analysis, circulating anti-MPO antibody expression was significantly higher in the TXA 20 and TXA 30 groups compared to the Control group (p = 0.001 and p = 0.001, respectively). Immunohistofluorescence staining revealed that D-dimer expression in the thrombotic femoral artery was significantly lower in the TXA 5, TXA 10, and TXA 20 groups compared to the Control group (p = 0.005; p = 0.018; p = 0.004, respectively), but significantly higher in the TXA 30 group than in the Control group (p = 0.044). Similarly, the expression of anti-fibrinogen antibody was significantly lower in the TXA 5, TXA 10, and TXA 20 groups compared to the Control group (p = 0.038; p = 0.003; p = 0.041, respectively). Western blot analysis showed no significant differences in the expression of anti-Ly6B.2, anti-fibrinogen, and anti-CD31 antibodies among the groups. Conclusions: The present study suggests that high-dose tranexamic acid (30 mg/kg) administration may increase circulating NETs and localized D-dimer levels, indicating a higher potential for thrombosis in a thrombosis mouse model. These findings imply that the prothrombotic effects of tranexamic acid may be dose-dependent and could vary based on underlying disease conditions. Therefore, the careful dosage adjustment of tranexamic acid may be necessary, particularly in patients at risk of thrombosis.

Un Yung Choi and Seung Hyun Lee. J. Microbiol. Biotechnol. 2024;34:1-10. https://doi.org/10.4014/jmb.2407.07039

Hyo Jin Park, Su Min Kim, Un Yung Choi & Lark Kyun Kim. BMB Reports 2024;57:431-40. https://doi.org/10.5483/BMBRep.2024-0045

Un Yung Choi, Youn Jung Choi, Shin-Ae Lee & Ji-Seung Yoo. BMB Reports 2024;57:256-61. https://doi.org/10.5483/BMBRep.2024-0011

The oral cavity is the major site for transmission of Kaposi’s sarcoma-associated herpesvirus (KSHV), but how KSHV establishes infection and replication in the oral epithelia remains unclear. Here, we report a KSHV spontaneous lytic replication model using fully differentiated, three-dimensional (3D) oral epithelial organoids at an air-liquid interface (ALI). This model revealed that KSHV infected the oral epithelia when the basal epithelial cells were exposed by damage. Unlike two-dimensional (2D) cell culture, 3D oral epithelial organoid ALI culture allowed high levels of spontaneous KSHV lytic replication, where lytically replicating cells were enriched at the superficial layer of epithelial organoid. Single cell RNA sequencing (scRNAseq) showed that KSHV infection induced drastic changes of host gene expression in infected as well as uninfected cells at the different epithelial layers, resulting in altered keratinocyte differentiation and cell death. Moreover, we identified a unique population of infected cells containing lytic gene expression at the KSHV K2-K5 gene locus and distinct host gene expression compared to latent or lytic infected cells. This study demonstrates an in vitro 3D epithelial organoid ALI culture model that recapitulates KSHV infection in the oral cavity, where KSHV undergoes the epithelial differentiation-dependent spontaneous lytic replication with a unique cell population carrying distinct viral gene expression.