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Molecular Markers for Interspecies Transmission of Avian Influenza Viruses in Mammalian Hosts
Lloren, Khristine Kaith S.,Lee, Taehyung,Kwon, Jin Jung,Song, Min-Suk MDPI 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.12
<P>In the last decade, a wide range of avian influenza viruses (AIVs) have infected various mammalian hosts and continuously threaten both human and animal health. It is a result of overcoming the inter-species barrier which is mostly associated with gene reassortment and accumulation of mutations in their gene segments. Several recent studies have shed insights into the phenotypic and genetic changes that are involved in the interspecies transmission of AIVs. These studies have a major focus on transmission from avian to mammalian species due to the high zoonotic potential of the viruses. As more mammalian species have been infected with these viruses, there is higher risk of genetic evolution of these viruses that may lead to the next human pandemic which represents and raises public health concern. Thus, understanding the mechanism of interspecies transmission and molecular determinants through which the emerging AIVs can acquire the ability to transmit to humans and other mammals is an important key in evaluating the potential risk caused by AIVs among humans. Here, we summarize previous and recent studies on molecular markers that are specifically involved in the transmission of avian-derived influenza viruses to various mammalian hosts including humans, pigs, horses, dogs, and marine mammals.</P>
최원석,Khristine Kaith S. Lloren,백윤희,송민석 대한백신학회 2017 Clinical and Experimental Vaccine Research Vol.6 No.2
Due to the increased frequency of interspecies transmission of avian influenza viruses, studies designed to identify the molecular determinants that could lead to an expansion of the host range have been increased. A variety of mouse-based mammalian-adaptation studies of avian influenza viruses have provided insight into the genetic alterations of various avian influenza subtypes that may contribute to the generation of a pandemic virus. To date, the studies have focused on avian influenza subtypes H5, H6, H7, H9, and H10 which have recently caused human infection. Although mice cannot fully reflect the course of human infection with avian influenza, these mouse studies can be a useful method for investigating potential mammalian adaptive markers against newly emerging avian influenza viruses. In addition, due to the lack of appropriate vaccines against the diverse emerging influenza viruses, the generation of mouse-adapted lethal variants could contribute to the development of effective vaccines or therapeutic agents. Within this review, we will summarize studies that have demonstrated adaptations of avian influenza viruses that result in an altered pathogenicity in mice which may suggest the potential application of mouse-lethal strains in the development of influenza vaccines and/or therapeutics in preclinical studies.
Jeong, Ju Hwan,Kim, Eun-Ha,Lloren, Khristine Kaith S.,Kwon, Jin Jung,Kwon, Hyeok-il,Ahn, Su Jeong,Kim, Young-Il,Choi, Won-Suk,Si, Young-Jae,Lee, Ok-Jun,Han, Hae Jung,Baek, Yun Hee,Song, Min-Suk,Choi, Elsevier 2019 Vaccine Vol.37 No.3
<P><B>Abstract</B></P> <P>Because H5N1 influenza viruses continuously threaten the public health, the WHO has prepared various clades of H5N1 mock-up vaccines as one of the measures for pandemic preparedness. The recent worldwide outbreak of H5Nx virus which belongs to clade 2.3.4.4 and of which H5N6 subtype belongs and already caused human infection also increases the need of pandemic vaccine for such novel emerging viruses. In this study, we evaluated the protective efficacy and immunogenicity of an egg-based and inactivated whole-virus H5N8 (IDCDC-RG43A) developed by CDC containing HA and NA gene of the parent virus A/gyrfalcon/Washington/41088-6/2014. Mice vaccinated two times elicited low to moderate antibody titer in varying amount of antigen doses against the homologous H5N8 vaccine virus and heterologous intra–clade 2.3.4.4 H5N6 (A/Sichuan/26221/2014) virus. Mice immunized with at least 3.0 µg/dose of IDCDC-RG43A with aluminum hydroxide adjuvant were completely protected from lethal challenge with the mouse-adapted H5N8 (A/Environment/Korea/ma468/2015, maH5N8) as well as cleared the viral replication in tissues including lung, brain, spleen, and kidney. Vaccinated ferrets induced high antibody titers against clade 2.3.4.4 H5N8/H5N6 viruses and the antibody showed high cross-reactivity to clade 2.2 H5N1 but not to clade 1 and 2.3.4 viruses as measured by hemagglutinin inhibition and serum neutralization assays. Furthermore, administration of the vaccine in ferrets resulted in attenuation of clinical disease signs and virus spread to peripheral organs including lung, spleen, and kidney from high dose challenge with maH5N8 virus. The protective and immunogenic characteristic of the candidate vaccine are essential attributes to be considered for further clinical trials as a pre-pandemic vaccine for a potential pandemic virus.</P>
( Yun Hee Baek ),( Hyo-soon Cheon ),( Su-jin Park ),( Khristine Kaith S. Lloren ),( Su Jeong Ahn ),( Ju Hwan Jeong ),( Won-suk Choi ),( Min-ah Yu ),( Hyeok-il Kwon ),( Jin-jung Kwon ),( Eun-ha Kim ),( 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.11
Recently, human infections caused by severe fever with thrombocytopenia syndrome virus (SFTSV), which can lead to fatality, have dramatically increased in East Asia. With the unavailability of vaccines or antiviral drugs to prevent and/or treat SFTSV infection, early rapid diagnosis is critical for prevention and control of the disease. Here, we report the development of a simple, rapid and sensitive portable detection method for SFTSV infection applying reverse transcription-loop mediated isothermal amplification (RT-LAMP) combined with one-pot colorimetric visualization and electro-free reaction platform. This method utilizes a pocket warmer to facilitate diagnosis in a resource-limited setting. Specific primers were designed to target the highly-conserved region of L gene of SFTSV. The detection limit of the RT-LAMP assay was approximately 10<sup>0</sup> viral genome copies from three different SFTSV strains. This assay exhibited comparable sensitivity to qRT-PCR and 10-fold more sensitivity than conventional RT-PCR, with a rapid detection time of 30 to 60 minutes. The RT-LAMP assay using SFTSV clinical specimens has demonstrated a similar detection rate to qRT-PCR and a higher detection rate compared to conventional RT-PCR. Moreover, there was no observed cross-reactive amplification of other human infectious viruses including Japanese Encephalitis Virus (JEV), Dengue, Enterovirus, Zika, Influenza and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This highly sensitive, electro- and equipment-free rapid colorimetric visualization method is feasible for resource-limited SFTSV field diagnosis.