Coding-complete genome sequence and phylogenetic analysis of Coxsackievirus B3 isolated from South Korea.

Whole-genome sequencing of a Coxsackievirus B3 strain isolated from the stool of a febrile patient with aseptic meningoencephalitis, South Korea, in 2002 was performed. This strain exhibits a high nucleotide sequence identity with various strains circulating in China from 2001 to 2019.

Small interfering RNA (siRNA)-based therapeutic applications against viruses: principles, potential, and challenges.

RNA has emerged as a revolutionary and important tool in the battle against emerging infectious diseases, with roles extending beyond its applications in vaccines, in which it is used in the response to the COVID-19 pandemic. Since their development in the 1990s, RNA interference (RNAi) therapeutics have demonstrated potential in reducing the expression of disease-associated genes. Nucleic acid-based therapeutics, including RNAi therapies, that degrade viral genomes and rapidly adapt to viral mutations, have emerged as alternative treatments. RNAi is a robust technique frequently employed to selectively suppress gene expression in a sequence-specific manner. The swift adaptability of nucleic acid-based therapeutics such as RNAi therapies endows them with a significant advantage over other antiviral medications. For example, small interfering RNAs (siRNAs) are produced on the basis of sequence complementarity to target and degrade viral RNA, a novel approach to combat viral infections. The precision of siRNAs in targeting and degrading viral RNA has led to the development of siRNA-based treatments for diverse diseases. However, despite the promising therapeutic benefits of siRNAs, several problems, including impaired long-term protein expression, siRNA instability, off-target effects, immunological responses, and drug resistance, have been considerable obstacles to the use of siRNA-based antiviral therapies. This review provides an encompassing summary of the siRNA-based therapeutic approaches against viruses while also addressing the obstacles that need to be overcome for their effective application. Furthermore, we present potential solutions to mitigate major challenges.

Role of cervids in the epidemiology of bovine ephemeral fever virus infection in the Republic of Korea: A cross-sectional retrospective study.

BACKGROUND: Bovine ephemeral fever (BEF) is a viral disease in cattle and buffaloes, with subclinical involvement in various ruminant species. OBJECTIVES: This study aimed to investigate bovine ephemeral fever virus (BEFV) transmission in deer in the Republic of Korea (ROK) and the potential risk factors associated with seropositivity. METHODS: We conducted a retrospective cross-sectional serological survey of neutralising antibodies against BEFV in cervid sera collected from the ROK. RESULTS: The seroprevalence of BEFV was estimated to be 10.8% (95% confidence interval [CI] = 8.5-14.1), demonstrating that exposure to this virus is prevalent among farmed and free-ranging cervids in the ROK. The results revealed that age class and geographic location affected seroprevalence. Older age and the presence of neighbouring ruminant farms were significant risk factors (odds ratio [OR] = 2.394, 95% CI = 1.195-4.796) and (OR = 1.533, 95% CI = 1.026-2.288), respectively. We also observed that the individual likelihood of positivity in the southern provinces was significantly higher than that in the northern provinces (OR = 1.744, 95% CI = 1.001-3.037). There were also significant differences in the seroprevalence of cervids between the western and eastern provinces (OR = 2.021, 95% CI = 1.047-3.900). Factors that were not significantly associated with BEFV antibody prevalence included herd size and species (p > 0.05). CONCLUSIONS: These results suggest that cervid species may serve as important reservoirs for the transmission of BEFV, highlighting the need for closer monitoring of BEFV infections in cervids in the ROK.

Seroprevalence and Epidemiological Risk Factors for Kasba Virus Among Sheep and Goats in South Korea: A Nationwide Retrospective Study.

Introduction: Kasba virus belongs to the Palyam serogroup of the Orbivirus genus and Reoviridae family. Kasba virus is the causative agent of many reproductive disorders in infected animals, which result in considerable economic losses, mainly in the cattle industry. The epidemiology of Kasba virus infection is poorly defined and remains unclear in South Korea. Material and Methods: This study investigated the prevalence of antibodies against Kasba virus in sheep and goats in South Korea. Individual, management, and regional risk factors associated with seropositivity were also evaluated. In addition, a retrospective serosurvey was conducted. Results: Serum samples from 28 out of 441 sheep or goat flocks (6.3%, 95% confidence interval (CI): 4.4-9.0%) and 115 out of 1003 animals (11.5%, 95% CI 9.6-13.6%) were positive for antibodies against Kasba virus. According to our results, a history of reproductive problems increased the probability of Kasba virus positivity. Preventive measures such as routine insecticide application decreased this probability. We observed significant differences in the prevalence of seropositivity between southern provinces and northern provinces and between western provinces and eastern provinces at the individual level. Conclusion: The virus was widely distributed among sheep and goats in South Korea, with seropositivity ranging from 6.8% in 2004 to 13.7% in 2008. The current study represents the first assessment of factors associated with Kasba virus seroprevalence in sheep and goats in South Korea.

Factors associated with seropositivity to Aino virus among sheep and goats in South Korea.

Aino virus infection is responsible for epizootic and/or sporadic outbreaks of abortions, stillbirths and premature delivery among pregnant ruminants. The epizootiology of Aino virus infection is poorly defined in South Korea, therefore our aim was to assess its seroprevalence among sheep and goats. We also wanted to evaluate management and regional risk factors that might influence the frequency of infection. Between 2012 and 2013, 26 of 331 flocks (7.9%) and 139 of 915 heads (15.2%) were found serologically positive. In 2018, when samples were again collected in the same regions, 35 of 308 flocks (11.4%) and 89 of 735 heads (12.1%) showed serum-neutralising antibodies against Aino virus. Our results revealed that the age class and history of reproductive problems in the flocks are connected to an increased risk of being positive. The management risk factor attributes showed that preventive measures, such as the routine application of insecticide in farms, decreased the odds for seropositivity to Aino virus (OR = 0.453, P = 0.001). We observed a significant difference in the individual likelihood of being positive in the southern and western provinces with respect to that in the northern and eastern provinces, respectively (OR = 2.199, P < 0.001 and OR = 2.177, P < 0.001). The results of this study may serve as a basis for future epizootic studies on Aino virus infection in South Korea.

Metabolic reprogramming as a novel therapeutic target for Coxsackievirus B3.

Coxsackievirus B3 (CVB3) is a single-stranded RNA virus that belongs to the Enterovirus genus. CVB3 is a human pathogen associated with serious conditions such as myocarditis, dilated cardiomyopathy, and pancreatitis. However, there are no therapeutic interventions to treat CVB3 infections. In this study, we found that CVB3 induced metabolic alteration in host cells through increasing glycolysis level, as indicated by an increase in the extracellular acidification rate (ECAR). CVB3-mediated metabolic alteration was confirmed by metabolite change analysis using gas chromatography-mass spectrometry (GC-MS). Based on findings, a strategy to inhibit glycolysis has been proposed to treat CVB3 infection. Indeed, glycolysis inhibitors (2-Deoxy-D-glucose, sodium oxide) significantly reduced CVB3 titers after CVB3 infection, indicating that glycolysis inhibitors can be used as effective antiviral agents. Taken together, our results reveal a novel mechanism by which CVB3 infection is controlled by regulation of host cell metabolism.

Seroepidemiology of Aino Virus in Farmed and Free-Ranging Cervids in the Republic of Korea.

Aino virus is an infectious, non-contagious, vector-borne agent that has been implicated in arthrogryposis-hydranencephaly syndrome in newborn cattle, sheep, and goats. Information about reservoirs and host animal species susceptible to Aino virus remains unclear. To further explore the role of cervids in Aino virus infection transmission, we investigated cervid sera to determine the prevalence of Aino virus-neutralizing antibodies and to identify factors correlated with antibody positivity. We screened cervid serum samples collected in the Republic of Korea to better understand infection patterns in this animal species. Overall, Aino virus infection was widespread; 75 of 716 (10.5%, 95% [95% CI] = 8.4-13.4) farmed-cervid serum samples collected from 292 herds contained antibodies to Aino virus. Serological evidence of Aino virus infection was demonstrated in 5 of 43 free-ranging cervids, accounting for a prevalence rate of ~11.6% (95% CI = 4.6-26.4). Our results revealed that age class and geographic location affected seroprevalence. The main risk factors associated with Aino virus seroprevalence were older age (> 2 years old, OR = 2.221, 95% CI = 1.209-4.079, P = 0.009 in adults), southern provinces (OR = 2.432, 95% CI = 1.445-4.093, P = 0.001), and western provinces (OR = 1.905, 95% CI = 1.041-3.488, P = 0.034). The results in this study suggest that cervid species might serve as important hosts for the transmission of Aino virus, highlighting the need for careful monitoring of Aino virus infections in cervids.

Radicicol Inhibits Chikungunya Virus Replication by Targeting Nonstructural Protein 2.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes a debilitating febrile illness characterized by persistent muscle and joint pain. The widespread distribution of transmission-competent vectors, Aedes species mosquitoes, indicates the potential risk of large-scale epidemics with high attack rates that can severely impact public health globally. Despite this, currently, there are no antivirals available for the treatment of CHIKV infections. Thus, we aimed to identify potential drug candidates by screening a chemical library using a cytopathic effect-based high-throughput screening assay. As a result, we identified radicicol, a heat shock protein 90 (Hsp90) inhibitor that effectively suppressed CHIKV replication by blocking the synthesis of both positive- and negative-strand viral RNA as well as expression of viral proteins. Interestingly, selection for viral drug-resistant variants and mutational studies revealed nonstructural protein 2 (nsP2) as a putative molecular target of radicicol. Moreover, coimmunoprecipitation and in silico modeling analyses determined that G641D mutation in the methyltransferase (MT)-like domain of nsP2 is essential for its interaction with cytoplasmic Hsp90ß chaperone. Our findings collectively support the potential application of radicicol as an anti-CHIKV agent. The detailed study of the underlying mechanism of action further contributes to our understanding of virus-host interactions for novel therapeutics against CHIKV infection.