• Korean Journal of Veterinary Service
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• v.46 no.3
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• pp.193-202
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• 2023

Porcine epidemic diarrhea is an infectious intestinal disease caused by the porcine epidemic diarrhea virus (PEDV). Especially, when suckling piglets are infected, the mortality rate is close to 100%. PEDV is classified into G1 and G2 types based on genetic differences. The G2 type PEDV outbreak in the United States in 2013 was highly pathogenic and contagious, and it has spread worldwide and caused continuous economic losses. Most commercial vaccines used are G1 type vaccines, and existing vaccines do not fully protect piglets due to genetic differences. In this study, we evaluated the safety of the newly developed G2 type attenuated HSGP vaccine strain by inoculating it into piglets and testing whether the vaccine virus spreads to the non-vaccinated, negative pigs and whether the vaccine reverts to its virulence during serial passage experiments. Each experiment lasted for 7 days for each passage, and fecal viral titers, clinical symptoms, and weight gain were measured daily. After the experiment, necropsy was performed to measure intestinal virus titer and pathological evaluation. As a result of the first passage, no transmission of the vaccine virus to negative pigs co-housed with vaccinated pigs was observed. In addition, after four consecutive passage experiments, the clinical symptoms and small intestine lesions were gradually alleviated, and no virus was detected in the feces in the fourth passage experiment. Therefore, it was concluded that the vaccine was safe without virulence reversion in accordance with the guidelines of the current licensing authority. However, further studies are needed on the genetic changes and biological characteristics of the mutant virus that occur during successive passages of the attenuated vaccine since the replication and clinical symptoms of the virus increased until the third passage during successive passages of the vaccine virus. Based on this study, it was concluded that virulence reversion and safety evaluation of attenuated vaccines through serial passage in target animals can be useful to evaluate the safety of attenuated viruses.

• Journal of Preventive Medicine and Public Health
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• v.55 no.2
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• pp.134-143
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• 2022

Objectives: Many governments have imposed-and are still imposing-mobility restrictions to contain the coronavirus disease 2019 (COVID-19) pandemic. However, there is no consensus on whether policy-induced reductions of human mobility effectively reduce the effective reproduction number (Rt) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several studies based on country-restricted data reported conflicting trends in the change of the SARS-CoV-2 Rt following mobility restrictions. The objective of this study was to examine, at the global scale, the existence of regional specificities in the correlations between Rt and human mobility. Methods: We computed the Rt of SARS-CoV-2 using data on worldwide infection cases reported by the Johns Hopkins University, and analyzed the correlation between Rt and mobility indicators from the Google COVID-19 Community Mobility Reports in 125 countries, as well as states/regions within the United States, using the Pearson correlation test, linear modeling, and quadratic modeling. Results: The correlation analysis identified countries where Rt negatively correlated with residential mobility, as expected by policymakers, but also countries where Rt positively correlated with residential mobility and countries with more complex correlation patterns. The correlations between Rt and residential mobility were non-linear in many countries, indicating an optimal level above which increasing residential mobility is counterproductive. Conclusions: Our results indicate that, in order to effectively reduce viral circulation, mobility restriction measures must be tailored by region, considering local cultural determinants and social behaviors. We believe that our results have the potential to guide differential refinement of mobility restriction policies at a country/regional resolution.

• Journal of Microbiology and Biotechnology
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• v.33 no.4
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• pp.441-448
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• 2023

Brucellosis is a contagious zoonotic disease that infects millions of people annually with hundreds of millions more being exposed. It is caused by Brucella, a highly infectious bacterial species capable of infecting humans with an estimated dose of 10-100 organisms. Sirtuin 1 (SIRT1) has been reported to contribute to prevention of viral diseases as well as a chronic infection caused by Mycobacterium bovis. Here, we investigated the role of SIRT1 in the establishment of Brucella abortus infection in both in vitro and in vivo systems using the reported SIRT1 activators resveratrol (RES), piceatannol (PIC), and ginsenoside Rg3 (Rg3). In RAW264.7 cells, SIRT1 activators did not alter the adherence of Brucella or Salmonella Typhimurium. However, reduced uptake of Brucella was observed in cells treated with PIC and Rg3, and survival of Brucella within the cells was only observed to decrease in cells that were treated with Rg3, while PIC treatment reduced the intracellular survival of Salmonella. SIRT1 treatment in mice via oral route resulted in augmented Brucella resistance for PIC and Rg3, but not RES. PIC treatment favors Th2 immune response despite reduced serum pro-inflammatory cytokine production, while Rg3-treated mice displayed high IL-12 and IFN-γ serum production. Overall, our findings encourage further investigation into the complete mechanisms of action of the different SIRT1 activators used as well as their potential benefit as an effective alternative approach against intracellular and extracellular pathogens.

• Journal of Veterinary Science
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• v.24 no.5
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• pp.54.1-54.13
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• 2023

Background: Porcine reproductive and respiratory syndrome virus (PRRSV) vaccines do not provide full cross-protection, mainly due to the virus genetic variability. Despite this, vaccines based on modified-live PRRSV (PRRSV-MLV) reduce the disease impact. Objectives: To assess the efficacy of two commercial vaccines-one based on PRRSV1 (PRRSV1-MLV) and another on PRRSV2 (PRRSV2-MLV)-against a Japanese PRRSV2 field strain. Methods: Two groups of three-week-old piglets were vaccinated (G1: PRRSV1-MLV; G2: PRRSV2-MLV) and two were kept as non-vaccinated (INF and CTRL). One month later, G1, G2, and INF were challenged with a PRRSV2 field strain. Results: After the challenge, clinical signs were only observed in INF. Moreover, the highest rectal temperatures and values for the area under the curve (AUC) were observed in INF. Regarding viral detection, both AUC and the proportion of positive samples in blood were higher in INF. In G1, viremic animals never reached 100%. At necropsy (21 d after the challenge), differences for titers among groups were only found in tonsils (G1 < G2 and INF). One animal (belonging to G1) was negative in all tissues. Regarding humoral responses, G1 and G2 seroconverted after vaccination, as detected in the corresponding enzyme-linked immunosorbent assay. Specific neutralizing antibodies (NA) against PRRSV1-MLV were already detected at 14 d after vaccination in G1, showing a significant booster after the challenge, while PRRSV2-MLV NA were detected in G2 at the end of the experiment. Conclusions: Despite genetic differences, PRRSV1-MLV has been demonstrated to confer partial protection against a Japanese PRRSV2 strain, at least as good as PRRSV2-MLV.

• Journal of Veterinary Science
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• v.24 no.5
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• pp.55.1-55.12
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• 2023

Background: Peste des petits ruminants (PPR), caused by the PPR virus (PPRV), is an acute and fatal contagious disease that mainly infects goats, sheep, and other artiodactyls. Peripheral blood mononuclear cells (PBMCs) are considered the primary innate immune cells. Objectives: PBMCs derived from goats were infected with PPRV and analyzed to detect the relationship between PPRV replication and apoptosis or the inflammatory response. Methods: Quantitative real-time polymerase chain reaction was used to identify PPRV replication and cytokines expression. Flow cytometry was conducted to detect apoptosis and the differentiation of CD4⁺ and CD8⁺ T cells after PPRV infection. Results: PPRV stimulated the differentiation of CD4⁺ and CD8⁺ T cells. In addition, PPRV induced apoptosis in goat PBMCs. Furthermore, apoptosis and the inflammatory response induced by PPRV could be suppressed by Z-VAD-FMK and Z-YVAD-FMK, respectively. Moreover, the virus titer of PPRV was attenuated by inhibiting caspase-1-dependent apoptosis and inflammation. Conclusions: This study showed that apoptosis and the inflammatory response play an essential role in PPR viral replication in vitro, providing a new mechanism related to the cell host response.

• Journal of Veterinary Science
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• v.25 no.3
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• pp.46.1-46.11
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• 2024

Importance: Rabies is a neglected tropical viral disease most often transmitted through the bite of an infected animal. Objective: This study assessed the level of knowledge, attitudes, and practices of the Shone Ttown community toward rabies. Methods: A survey-based cross-sectional study was conducted in Shone town, Ethiopia, from November 2022 to April 2023. Woreda was selected purposefully, while Kebeles and the study populations were selected by simple random sampling. Four hundred and sixteen respondents were interviewed using a semi-structured questionnaire. Results: All respondents had heard about rabies from different sources, with the majority hearing from informal sources (62%). Approximately 51.9%, 0.7%, and 47.4% of individuals were aware of saliva contact, rabid animal bites, and both as means of transmission, respectively. The survey showed that 64.4% of participants knew the 100% fatal nature of rabies once the clinical signs developed, and 35.6% did not. Approximately 51.4% of respondents agreed that killing stray dogs was an effective method for rabies prevention. In this study, 72.6% of the respondents had contact with pets, and 36.8% of the interviewees had vaccinated their dogs. Only the educational level (p = 0.03) was associated with knowledge of the transmission route. Age (p = 0.04) and educational level (p = 0.01) had a statistically significant association with knowledge of the risk of not vaccinating dogs. Conclusions and Relevance: A lack of formal education in the communities, low levels of education, and the majority of respondents acquiring their knowledge from unofficial sources are important contributors to the low levels of awareness.

• IMMUNE NETWORK
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• v.23 no.2
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• pp.18.1-18.15
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• 2023

It has been reported that some exercise could enhance the anti-viral antibody titers after vaccination including influenza and coronavirus disease 2019 vaccines. We developed SAT-008, a novel digital device, consists of physical activities and activities related to the autonomic nervous system. We assessed the feasibility of SAT-008 to boost host immunity after an influenza vaccination by a randomized, open-label, and controlled study on adults administered influenza vaccines in the previous year. Among 32 participants, the SAT-008 showed a significant increase in the anti-influenza antibody titers assessed by hemagglutination-inhibition test against antigen subtype B Yamagata lineage after 4 wk of vaccination and subtype B Victoria lineage after 12 wk (p<0.05). There was no difference in the antibody titers against subtype "A." The SAT-008 also showed significant increase in the plasma cytokine levels of IL-10, IL-1β, and IL-6 at weeks 4 and 12 after the vaccination (p<0.05). A new approach using the digital device may boost host immunity against virus via vaccine adjuvant-like effects.

• IMMUNE NETWORK
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• v.21 no.1
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• pp.9.1-9.8
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• 2021

The most important characteristics of coronavirus disease 2019 (COVID-19) transmission that makes it difficult to control are 1) asymptomatic and presymptomatic transmission, 2) low incidence or lack of dominant systemic symptoms such as fever, 3) airborne transmission that may need a high infectious dose, and 4) super-spread events (SSEs). Patients with COVID-19 have high viral loads at symptom onset or even a few days prior to symptom onset, and most patients with COVID-19 have only mild respiratory symptoms or merely pauci-/null-symptoms. These characteristics of the virus enable it to easily spread to the community because most patients are unaware of their potential infectivity, and symptom-based control measures cannot prevent this type of transmission. Furthermore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is also capable of airborne transmission in conditions such as aerosol-generating procedures, under-ventilated indoor spaces, and over-crowded areas. In this context, universal mask-wearing is important to prevent both outward and inward transmission until an adequate degree of herd immunity is achieved through vaccination. Lastly, the SSEs of SARS-CoV-2 transmission emphasize the importance of reducing contacts by limiting social gatherings. The above-mentioned transmission characteristics of SARS-CoV-2 have culminated in the failure of long-lasting quarantine measures, and indicate that only highly effective vaccines can keep the communities safe from this deadly, multifaceted virus.

• IMMUNE NETWORK
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• v.21 no.6
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• pp.42.1-42.20
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• 2021

Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.

• Journal of Ginseng Research
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• v.48 no.4
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• pp.384-394
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• 2024

Background: Herpes simplex virus type 1 (HSV-1), known to latently infect the host's trigeminal ganglion, can lead to severe herpes encephalitis or asymptomatic infection, potentially contributing to neurodegenerative diseases like Alzheimer's. The virus generates reactive oxygen species (ROS) that significantly impact viral replication and induce chronic inflammation through NF-κB activation. Nuclear factor E2-related factor 2 (Nrf2), an oxidative stress regulator, can prevent and treat HSV-1 infection by activating the passive defense response in the early stages of infection. Methods and results: Our study investigated the antiviral effects of ginsenoside Rg5, an Nrf2 activator, on HSV-1 replication and several host cell signaling pathways. We found that HSV-1 infection inhibited Nrf2 activity in host cells, induced ROS/NF-κB signaling, and triggered inflammatory cytokines. However, treatment with ginsenoside Rg5 inhibited ROS/NF-κB signaling and reduced inflammatory cytokines through NRF2 induction. Interestingly, the Nrf2 inhibitor ML385 suppressed the expression of NAD(P)H quinone oxidoreductase 1(NQO1) and enhanced the expression of KEAP1 in HSV-1 infected cells. This led to the reversal of VP16 expression inhibition, a protein factor associated with HSV-1 infection, thereby promoting HSV-1 replication. Conclusion: These findings suggest for the first time that ginsenoside Rg5 may serve as an antiviral against HSV-1 infection and could be a novel therapeutic agent for HSV-1-induced neuroinflammation.