Dae Gwin Jeong

Shiga Toxins as Multi-Functional Proteins: Induction of Host Cellular Stress Responses, Role in Pathogenesis and Therapeutic Applications.

Shiga toxins (Stxs) produced by Shiga toxin-producing bacteria Shigella dysenteriae serotype 1 and select serotypes of Escherichia coli are primary virulence factors in the pathogenesis of hemorrhagic colitis progressing to potentially fatal systemic complications, such as hemolytic uremic syndrome and central nervous system abnormalities. Current therapeutic options to treat patients infected with toxin-producing bacteria are limited. The structures of Stxs, toxin-receptor binding, intracellular transport and the mode of action of the toxins have been well defined. However, in the last decade, numerous studies have demonstrated that in addition to being potent protein synthesis inhibitors, Stxs are also multifunctional proteins capable of activating multiple cell stress signaling pathways, which may result in apoptosis, autophagy or activation of the innate immune response. Here, we briefly present the current understanding of Stx-activated signaling pathways and provide a concise review of therapeutic applications to target tumors by engineering the toxins.

Canine susceptibility to human influenza viruses (A/pdm 09H1N1, A/H3N2 and B).

We investigated the infectivity and transmissibility of the human seasonal H3N2, pandemic (pdm) H1N1 (2009) and B influenza viruses in dogs. Dogs inoculated with human seasonal H3N2 and pdm H1N1 influenza viruses exhibited nasal shedding and were seroconverted against the viruses; this did not occur in the influenza B virus-inoculated dogs. Transmission of human H3N2 virus between dogs was demonstrated by observing nasal shedding and seroconversion in naïve dogs after contact with inoculated dogs. The seroprevalence study offered evidence of human H3N2 infection occurring in dogs since 2008. Furthermore, serological evidence of pdm H1N1 influenza virus infection alone and in combination with canine H3N2 virus was found in the serum samples collected from field dogs during 2010 and 2011. Our results suggest that dogs may be hosts for human seasonal H3N2 and pdm H1N1 influenza viruses.

Detection of Severe Acute Respiratory Syndrome-Like, Middle East Respiratory Syndrome-Like Bat Coronaviruses and Group H Rotavirus in Faeces of Korean Bats

Summary Bat species around the world have recently been recognized as major reservoirs of several zoonotic viruses, such as severe acute respiratory syndrome coronavirus (SARS‐CoV), Middle East respiratory syndrome coronavirus (MERS‐CoV), Nipah virus and Hendra virus. In this study, consensus primer‐based reverse transcriptase polymerase chain reactions (RT‐PCRs) and high‐throughput sequencing were performed to investigate viruses in bat faecal samples collected at 11 natural bat habitat sites from July to December 2015 in Korea. Diverse coronaviruses were first detected in Korean bat faeces, including alphacoronaviruses, SARS‐CoV‐like and MERS‐CoV‐like betacoronaviruses. In addition, we identified a novel bat rotavirus belonging to group H rotavirus which has only been described in human and pigs until now. Therefore, our results suggest the need for continuing surveillance and additional virological studies in domestic bat.

Complete mitochondrial genome of the Pacific white-sided dolphin Lagenorhynchus obliquidens (Cetacea: Delphinidae)

The Pacific white-sided dolphin (Lagenorhynchus obliquidens Gill, 1865) is one of the most abundant, widely distributed delphinids in the North Pacific Ocean, whose existence is threatened by fisheries and environmental contamination. Herein, we report the first complete mitochondrial genome of L. obliquidens. The 16,392-bp sequenced genome exhibited typical cetacean mitochondrial gene arrangement, consisted of the typical set of 37 genes, one replication origin, and a D-loop. As expected, the genome displayed the highest similarity with that of Cephalorhynchus heavisidii and was distinct from that of L. albirostris. Multigene phylogeny also revealed that L. obliquidens was closely related to C. heavisidii, thus suggesting that the genus Lagenorhynchus is polyphyletic, in accordance with the results of recent molecular phylogenetic studies. The results provide information fundamental for genetic and conservation studies for L. obliquidens.

Recent outbreaks of highly pathogenic avian influenza viruses in South Korea

Outbreaks of H5 highly pathogenic avian influenza viruses (HPAIVs) have caused economic loss for the poultry industry and posed a threat to public health. In South Korea, novel reassortants of HPAIVs such as H5N6 and H5N8 had been circulating in poultry. Here, we will discuss the identity of recent novel reassortants of Korean H5 HPAIVs and the recent advances in vaccine development, which will be useful for controlling HPAIV transmission in poultry and for effectively preventing future epidemics and pandemics.

Outer membrane vesicles harboring modified lipid A moiety augment the efficacy of an influenza vaccine exhibiting reduced endotoxicity in a mouse model

Abstract Influenza is an acute respiratory disease and a major health problem worldwide. Since mucosal immunity plays a critical role in protection against influenza virus infection, mucosal immunization is considered a promising vaccination route. However, except for live-attenuated vaccines, there are no effective killed or recombinant mucosal influenza vaccines to date. Outer membrane vesicles (OMVs) are nano-sized vesicles produced by gram-negative bacteria, and contain various bacterial components capable of stimulating the immune system of the host. We generated an OMV with low endotoxicity (fmOMV) by modifying the structure of the lipid A moiety of lipopolysaccharide and investigated its effect as an intranasal vaccine adjuvant in an influenza vaccine model. In this model, fmOMV exhibited reduced toll-like receptor 4-stimulating activity and attenuated endotoxicity compared to that of native OMV. Intranasal injection of the vaccine antigen with fmOMV significantly increased systemic antibody and T cell responses, mucosal IgA levels, and the frequency of lung-resident influenza-specific T cells. In addition, the number of antigen-bearing CD103+ dendritic cells in the mediastinal lymph nodes was significantly increased after fmOMV co-administration. Notably, the mice co-immunized with fmOMV showed a significantly higher protection rate against challenge with a lethal dose of homologous or heterologous influenza viruses without adverse effects. These results show the potential of fmOMV as an effective mucosal adjuvant for intranasal vaccines.

Determination of the haplotype and complete mitochondrial genome of the leatherback turtle Dermochelys coriacea (Testudines: Dermochelyidae) found in the vicinity of Korea

Although several strandings of the leatherback turtle (Dermochelys coriacea Vandelli, 1761) have been reported in Korea, its haplotype or mitogenome have yet to be investigated. Herein, we report the first complete mitogenome of D. coriacea. The 16,501-bp sequenced mitogenome is similar to those of other marine turtles, and the particular genetic features reported in birds and turtles were also found in ND3 and ATP8. The comparison of the control region verified that D. coriacea stranded in Korea belonged to the haplotype JD1 (identical to haplotypes I and Dc9.1). Multigene phylogeny revealed that D. coriacea was well separated from other Cheloniidae species, and the overall tree topology was congruent with the recent phylogenetic analysis of marine turtles. These results provide information fundamental for genetic and conservation studies on leatherbacks, especially the critically endangered West Pacific Ocean subpopulation.

Nontoxic outer membrane vesicles efficiently increase the efficacy of an influenza vaccine in mice and ferrets

In this study, we developed a further-modified outer membrane vesicle (fmOMV) from the ΔmsbB/ΔpagP mutant of Escherichia coli transformed with the plasmid, pLpxF, in order to use it as an adjuvant for pandemic H1N1 (pH1N1) influenza vaccine. We evaluated the efficacy of the pH1N1 influenza vaccine containing the fmOMV in animal models as compared to the commercial adjuvants, alum or AddaVaxTM. The fmOMV-adjuvanted pH1N1 influenza vaccine induced a significant increase in the humoral immunity; however, this effect was less than that of the AddaVaxTM. The fmOMV-adjuvanted vaccine displayed pronounced an enhanced protective efficacy with increased T cell immune response and reduced the viral load in the lungs of the infected mice after challenging them with a lethal dose of the homologous virus. Moreover, it resulted in a significantly higher cross-protection against heterologous virus challenge than that of the pH1N1 vaccine with alum or with no adjuvants. In ferrets, the fmOMV-adjuvanted vaccine elicited a superior antibody response based on the HI titer and efficiently protected the animals from the lethal viral challenges. Taken together, the nontoxic fmOMV could be a promising adjuvant for inducing robust T cell priming into the pH1N1 vaccine and might be broadly applicable to the development of preventive measures against influenza virus infection.

Complete Genome Sequence of an Avian H1N1 Influenza Virus Strain Isolated from Migratory Birds in the Republic of Korea

ABSTRACT Here, we report the complete genome sequence of an H1N1 avian influenza virus (AIV), which was isolated from the feces of migratory birds in the Republic of Korea during the winters of 2014 and 2015. Full-genome sequencing and phylogenetic analysis revealed that all genome segments belonged to the Eurasian lineage.

Genetic Characterization of an Ancestral Strain of the Avian-Origin H3N2 Canine Influenza Virus Currently Circulating in East Asia.

H3N2 canine influenza virus emerged in South Korea in 2007 and subsequently spread to China and Thailand, causing epidemic or endemic respiratory diseases in dogs. Through intermammalian species transmission, the virus has also infected cats. However, no direct evidence of significant genetic evolution has been reported since its first emergence. Here, we describe in depth the genetic and molecular characteristics of the ancestral strain (i.e., the first virus isolate from South Korea) of the H3N2 canine influenza virus currently circulating in East Asia.