A novel human coronavirus was identified in Saudi Arabia and Qatar as the causative agent of severe acute respiratory diseases in 2012. The virus was termed Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and is taken notice of important coronavirus caused severe diseases to human after the outbreak of severe acute respiratory syndrome (SARS) coronavirus. There is a lot of unknown characterization regarding MERS-CoV because of less than one year after finding the first case. MERS-CoV was related to the 2C betacoronavirus clade and is closely related to Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5. Thus, bats are thought to be natural hosts of this virus. Recently, there were reports supposed to be cases of human to human infection. There are growing concerns about spread of infection.

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Severe fever with thrombocytopenia syndrome (SFTS) is characterized by sudden onset of fever, leukopenia, thrombocytopenia, and gastrointestinal tract symptoms and approximately 12% of patients die from disseminated intravascular coagulation and/or multiple organ failures. Agent of the disease is a novel bunyavirus SFTS virus, and is transmitted by bite of a possible vector tick, Haemaphysalis longicornis, and through direct contact with virus-containing patient body fluids, or through unknown routes. SFTS case reports have been limited in China, and more than two thousand cases were reported in 2011 and 2012. In late 2012, a woman living in Yamaguchi prefecture in Japan showed symptoms reminiscent of those of SFTS and died 6 days after the onset of symptoms. Virus was isolated from her acute serum in Vero cells and a next generation-sequencing identified it as SFTS virus. SFTS viral genome and proteins were detected in the patient's serum. Based on the first demonstration of SFTS in Japan, a retrospective study started. Until March of 2013, totally 8 patients were diagnosed as having SFTS and the most early case was in 2005. Phylogenetic analysis of virus sequences revealed that Japanese isolates form an independent branch distinct from Chinese isolates, indicating that SFTS has been present not only in China but also in Japan.

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Flaviviruses such as Japanese encephalitis virus, West Nile virus, yellow fever virus, dengue virus, and tick-borne encephalitis virus belong to a family Flaviviridae. These viruses are transmitted to vertebrates by infected mosquitoes or ticks, producing diseases, which have a serious impact on global public health. Reverse genetics is a powerful tool for studying the viruses. Although infectious full-length clones have been obtained for multiple flaviviruses, their early-stage development had the difficulty because of the instability problem of the viral cDNA in E. coli. Several strategies have been developed to circumvent the problem of infectious clone instability. The current knowledge accumulated on reverse genetics system of flaviviruses and its application are summarized in this review.

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A global expansion of Hepatitis B virus (HBV) infection continues still now, and it poses a still big problem. Since the Australia antigen was discovered, HBV research has been continued by various methods, such as clinical medicine and epidemiology. However, the simple and efficient infection experimental systems (in vitro and in vivo) have not been established, because the host range of HBV is narrow. Therefore, the techniques of reverse genetics have contributed to HBV research greatly. We have established the HBV clones of various genotypes from the chronic hepatitis B patients, and have analyzed using the techniques of reverse genetics. Based on our results, it has become clear gradually how HBV pathogenesis related to the genotypes. In this paper, we would like to introduce the outline of research analyzed by reverse genetics about HBV.

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[in Japanese]

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Recent rapid developments in Asian and African countries bring an opportunity of cross-species transmission of pathogens through unprecedented contacts between people and wild animals. Furthermore, increase of global exchanges of people and products facilitates a rapid spread of infectious diseases worldwide. China has an enormous population with diverse ethnic groups within its wide territory; furthermore, it is experiencing very rapid urbanization. These conditions make China a potential epicenter of emerging infectious diseases. One good example is the SARS incidence in 2003. Therefore, it is essential to include China in a network of research groups of infectious diseases. Here we summarize the ongoing collaborations between the Institute of Medical Science, the University of Tokyo, and its Chinese counterparts.

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Tohoku University Graduate School of Medicine has established the Tohoku-RITM Collaborative Research Center on Emerging and Re-emerging Diseases at Research Institute for Tropical Medicine (RITM) in the Philippines in 2008. Our aim of the center is to conduct operational researches, which can contribute to control of infectious diseases in the Philippines. Therefore most of our researches in the Philippines are being conducted in the fields. Main research themes include severe acute respiratory infections in children, influenza disease burden study, molecular epidemiology of rabies, and viral etiology of acute diarrhea. The study on severe acute respiratory infections in children in Leyte Island has recruited hospitalized cases with severe pneumonia. We showed that enterovirus 68 was one of important causative agents in severe pneumonia cases. We also conducted other analyses including molecular epidemiology of respiratory syncytial virus (RSV) and pathogenesis of human rhinoviruses (HRV). Based on these studies, we initiated more comprehensive researches in the Philippines since 2010.

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Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections (RCC-ERI) was established in 2005 as a research collaboration center cooperated by Research Institute for Microbial Diseases (RIMD), Osaka University and Department of Medical Sciences, Ministry of Public Health of Thailand. In addition, Mahidol-Osaka Center for Infectious Diseases (MOCID) was established in 2010, also as another research collaboration center cooperated by RIMD, Osaka University and Faculty of Tropical Medicine, Mahidol University. Epidemiological and basic studies on human pathogenic viruses have been conducted in RCC-ERI and MOCID. In this report, brief overviews of the research activities of both centers, as well as the phenotypic studies on the envelope glycoproteins of HIV-1 Thai strains that have been performed at RCC-ERI, are presented.
SATREPS is a Japanese government program by the Japan Science and Technology Agency (JST) and the Japan International Cooperation Agency (JICA) that promotes international joint research targeting global issues. Our research group at RIMD have collaborated with the Ministry of Public Health - National Institute of Health (NIH) and Mahidol University in Thailand from 2008 as a four-years project. Our aim on this collaboration is to generate human monoclonal antibodies neutralizing infectious viral agents, hopefully to apply them to clinical field as “therapeutic antibodies”. Here we introduce our trials in this project, especially on the generation of human monoclonal antibodies against dengue virus as well as against influenza virus that have been performed as collaboration between Thai and Japanese research groups.

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Kobe-Indonesia Collaborative Research Center was established in Institute of Tropical Disease (ITD), Airlangga University, Surabaya, Indonesia in 2007 under the program of ''Founding Research Centers for Emerging and Reemerging Infectious Diseases'' supported by the Ministry of Education, Culture, Sports, Science and Technology, Japan, and then it has been under the Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) since 2010. Japanese researchers have been stationed at ITD, conducting joint researches on influenza, viral hepatitis, dengue and infectious diarrhea. Also, another Japanese researcher has been stationed at Faculty of Medicine, University of Indonesia, Jakarta, carrying out joint researches on'' Identification of anti-hepatitis C virus (HCV) substances and development of HCV and dengue vaccines'' in collaboration with University of Indonesia and Airlangga University through the Science and Technology Research Partnership for Sustainable Development (SATREPS) supported by the Japan Science and Technology Agency (JST) and Japan International Cooperation Agency (JICA) since 2009. In this article, we briefly introduce the background history of Kobe University Research Center in Indonesia, and discuss the research themes and outcomes of J-GRID and SATREPS activities.

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Institute of Tropical Medicine, Nagasaki University (NEKKEN) and National Institute of Hygiene and Epidemiology, Vietnam (NIHE) jointly conducted a project from 2006 on Emerging and Re-emerging Infectious Diseases (ERID) granted by the Ministry of Education, Science, Culture and Technology (MEXT) of Japan. Fifteen independent researches have been carried out by 7 scientists who stationed in the Vietnam Research Station (VRS), and by approximately 60 visiting scientists. A wide variety of viruses have been studied in the research activities in the VRS, of those, topics of'' Nipah virus infection in bats in Vietnam'', ''Nam Dinh virus, a newly discovered insect nidovirus'', and'' Risk factors of dengue fever in southern Vietnam'' were summarized. It is important to develop a mechanism to facilitate young scientists to use the VRS in their research works, and then a scope to establish the VRS as a gateway to a successful career path for young scientists in the field of the infectious diseases would be realized.

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The Institute of Tropical Medicine, Kenya Research Station, Nagasaki University was established by a fund of the Ministry of Education (MEXT) in 2005. Currently, the station has been on ''The Clinical and Epidemiological Research Program of Tropical Medicine and Emerging Infectious DiseasesEstablishment of Education and Research System between Africa and Japan- ''. The project has been supported by about 20 Japanese staff and 85 Kenyan staff, and in the research station, 10 research teams have worked on their researches for the prevention of tropical medicine and emerging diseases collaborating with other researches and The JICA Grassroots Technical Cooperation Project has also started in 2012. In April 2010, Nagasaki University, Africa Station has been established along with Kenya Research Station, and it made possible for other faculties to join research in Kenya. School of Dentistry has started oral health survey in Mbita, while School of Fishery, School of Engineering and School of Health Science have a plan of a joint project targeting areas by Lake Victoria. Our aim is to develop a foundation which enables all researchers from different fields to carry out their research for improvement health and living standards of the locals.

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Ghana-Tokyo Medical and Dental University Research Collaboration Center has been established since 2008 when our Program was chosen together with the Program in the Philippines proposed by Tohoku University as an additional small-scale research center of the Overseas Research Program on Emerging and Reemerging Diseases that is funded by the Ministry of Education, Culture, Sports, Science and Technology of the Japanese Government and started in 2005. This 5-year government-supported Program has changed its name to develop into a more active world-level program called Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) and entered the second 5-year phase in 2010, and our Program is playing an important role among other research centers located in Asia and Africa. Currently, two research projects are carried out in parallel in Noguchi Memorial Institute for Medical Research by Tokyo Medical and Dental University: one is a J-GRID project and the other is the one of Science and Technology Research Partnership for Sustainable Development (SATREPS) which is a joint project between Japan International Cooperation Agency (JICA) and Japan Science and Technology Agency (JST). This special article is describing what these two projects are all about.

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[in Japanese]

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[in Japanese]

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Poliovirus (PV) is a small non-enveloped virus belonging to the family Picornaviridae, and is the causative agent of poliomyelitis. With established vaccines, the global eradication program for poliomyelitis is ongoing by the World Health Organization since 1988. In the eradication program, antivirals are anticipated to have some roles in the endgame and post-eradication era of PV. During our search for potent anti-PV compounds, we identified candidate compounds that are associated with a common resistance mutation in viral protein 3A similar to enviroxime (designated as enviroxime-like compounds). Recently, PIK93, an inhibitor of host phosphatidylinositol 4-kinase III beta (PI4KB), was identified as a potent anti-enterovirus compound (Hsu et al., Cell 141:799-811). We found that PIK93 is an enviroxime-like compound, and showed that T-00127-HEV1, which is a novel enviroxime-like compound identified in high-throughput screening, is a specific PI4KB inhibitor. We also showed that PI4KB is an enterovirus-specific host factor required for its viral RNA replication. Analysis of anti-enterovirus compounds would unravel novel host factors that could serve as promising antiviral targets of prophylaxis and therapy of the infection.

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The rotavirus genome is composed of 11 gene segments of double-stranded (ds)RNA. Reverse genetics is the powerful and ideal methodology for the molecular analysis of virus biology, which enables the virus genome to be artificially manipulated. Although reverse genetics systems exist for nearly all major groups of RNA viruses, development of such a system for rotaviruses is more challenging owing in part to the technical complexity of manipulation of their multi-segmented genome. A breakthrough in the field of rotavirus reverse genetics came in 2006, when we established the first reverse genetics system for rotaviruses, which is a partially plasmid-based system that permits replacement of a viral gene segment with the aid of a helper virus. Although this helper virus-driven system is technically limited and gives low levels of recombinant viruses, it allows alteration of the rotavirus genome, thus contributing to our understanding of these medically important viruses. In this review, I describe the development and application of our rotavirus reverse genetics system, and its future perspectives.

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