Development of PCR method had a great impact on studies on viruses in water environment, and now it makes possible to determine various kind of viruses from river, marine water and water/wastewater treatment systems, though there are still needs to improve accuracy of quantification. Now we know that river water may contain 1000copy/L of norovirus. The infectious risk management for recreational water has been left and not updated, hence we need develop better management system based on scientific knowledge.

Influenza A virus (IAV) recognizes terminal sialic acid of sialoglyco-conjugates on host cells through the viral envelope glycoprotein hemagglutinin (HA), followed by initiation of entry into the cells. Molecular species of sialic acid are largely divided into two moieties: N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). A receptor for IAV infection generally means Neu5Ac. Almost all equine IAVs and some human, swine, and duck IAVs bind not only to Neu5Ac but also to Neu5Gc. In nonhuman animals, Neu5Gc has been detected in swine and equine tracheas and the duck colon, which are the main replication sites of mammalian and avian IAVs. Therefore, Neu5Gc in these sites has been suggested to be a functional receptor for IAV infection. Humans cannot synthesize Neu5Gc due to a genetic defect of the Neu5Gc-synthesizing enzyme. We evaluated the receptor function of Neu5Gc in IAV infection in human cells. Our results indicated that Neu5Gc expression on the surface of human cells is not a functional receptor for IAV infection and that it has a negative effect on infectivity of IAV possessing Neu5Gc binding ability. IAV also binds to non-sialo 3-O-sulfated galactosylceramide (sulfatide). Sulfatide has been suggested to be a functional receptor for IAV infection. However, we have shown that sulfatide is not a functional receptor for IAV infection and that the binding of HA with sulfatide enhances progeny virus production. It is expected that functions of these glyco-molecules can be used in prevention and development of new drugs against IAV.

microRNA-122 (miR-122) is an abundant, liver-specific miRNA that regulates gene expression post-transcriptionally, typically by binding to the 3' untranslated region (UTR) of mRNAs, repressing their translation and mediating their degradation. Hepatitis C virus (HCV) is uniquely dependent on miR-122. Similar to conventional miRNA action, miR-122 recruits Argonaute-2 (AGO2) protein to the 5' UTR of the viral genome. However, in contrast to typical miRNA function, this stabilizes HCV RNA and slows its decay in infected cells. We found that HCV RNA is degraded primarily by the cytoplasmic 5' exonuclease XRN1 and that miR-122 acts to protect the viral RNA from XRN1-mediated 5' exonucleolytic decay. However, HCV replication still requires miR-122 in XRN1-depleted cells, suggesting additional functions. We also showed that miR-122 enhances HCV RNA synthesis by reducing viral genomes engaged in translation while increasing the fraction available for RNA synthesis. In this review, we summarize the recent progress on the regulatory mechanisms of HCV genome replication by miR-122.

Viroporins are small and hydrophobic viral proteins that form pores on host cell membranes, and their expression can increase the permeability of cellular membranes and the production of progeny virus particles. JC virus (JCV) is the causative agent of progressive multifocal leukoenchephalopathy (PML). We demonstrate that JCV Agno, which is the small and hydrophobic protein, andincreases the plasma membrane permeability and virion release, acts as a viroporin. We also demonstrate that an interaction of Agno with a host cellular protein regulates the viroporin activity of Agno. These findings indicate a new paradigm in virus-host interactions regulating viroporin activity and viral replication.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV), a novel phlebovirus reported to be endemic to China in 2011. In Japan, the first SFTS patient was identified during the autumn of 2012; since then, over 100 SFTS patients have been reported. The SFTSV has been identified throughout Japan over the past two years; however, SFTS patients are specifically localized to western Japan. The clinical symptoms of SFTS include fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, and various other symptoms, including muscular symptoms, neurological abnormalities, and coagulopathy. SFTS is often accompanied by hemophagocytic syndrome. The histopathological findings are characterized by necrotizing lymphadenitis, with infiltration of the virus-infected cells to the local lymph nodes. Pathophysiological analyses of SFTS include studies regarding the kinetics of cytokine production and immune responses in patients with SFTS and in SFTSV-infection animal models. This article aimed to survey the history of SFTS in Japan and to review the clinical, epidemiological, and virological aspects of SFTS and SFTSV infection.

Although a globe box-type highly contained laboratory with the internationally-recognized biosafety level-4 standards has been constructed in the Murayama Annex, the National Institute of Infectious Diseases, Tokyo, Japan (NIID) in 1981, the laboratory has never been operated as BSL-4 laboratory since its construction. Furthermore, there are no other BSL-4 laboratories in operation in Japan. The evidence indicates that infectious BSL-4 pathogens such as Ebola and Marburg viruses cannot be manipulated in Japan, making it impossible to study the BSL-4 pathogens using the infectious viruses. A large-scale outbreak of ebolavirus disease (EVD) has occurred in the western Africa such as Guinea, Sierra Leone, and Liberia. Furthermore, the highly pathogenic pathogens' infectious diseases outbreaks such as SARS, Nipah encephalitis, Middle East respiratory syndrome (MERS) have emerged in the world. However, BSL-4 laboratories are not present in Japan, making it difficult to study these pathogens and infectious diseases. Because these emerging virus infections are caused by the zoonotic pathogens, the eradiation and the elimination of these infectious diseases are impossible. We need to develop the diagnostics, therapeutics, and preventive measures based on the studies of the highly pathogenic pathogens more in detail using the infectious microbes. Therefore, BSL-4 in operation in Japan is required to minimize the risk of and combat these emerging highly pathogenic pathogens' infectious diseases.

Ebola virus causes Ebola virus disease (EVD) with high case fatality rates in humans and has caused sporadic outbreaks with less than 500 cases. An EVD outbreak in West Africa, which probably started at the end of 2013, has an unprecedented large-scale with more than 20,000 cases including more than 10,000 death and is still ongoing as of May 2015. National Institute of Infectious Diseases has developed laboratory diagnostic methods of EVD to detect pathogens (genes or protein) and antibodies. The methods have been recently used for suspected cases approximately once a year before the outbreak in West Africa, but after the outbreak for 7 times within this 6 months for suspected cases coming back from 3 countries of West Africa to Japan.

Hepatitis C virus (HCV) infection often causes intrahepatic diseases, such as chronic hepatitis, liver chirrohsis, and hepatocellular carcinoma (HCC). Moreover, HCV infection exhibits various extrahepatic manifestations, such as thyroiditis, glucose and lipid metabolic disorder, and iron metabolic disorder. HCV infection is often associated with type 2 diabetes, involving hepatic fibrosis and poor prognosis. Type 2 diabetes increases the risk of HCC. We have been investigating molecular mechanisms of HCV-induced glucose metabolic disorder and we reported that HCV infection promotes hepatic gluconeogenesis through forkhead box O1 (FoxO1)-dependent pathway and that HCV infection suppresses the cell surface expression of glucose transporter 2 (GLUT2), resulting in suppression of glucose uptake. We have found that HCV NS5A protein plays important roles in these two independent pathways. Here we discuss the roles of HCV NS5A in HCV-induced glucose metabolic disorder.

Most of the reported dominant disease-resistance genes in plants, R genes, encode NB-LRR immune receptors. Plant genomes carry many NB-LRR type R genes that recognize specific pathogens and induce resistance against them. Thus, this immune system in plants is thought to perform similar functions as the adaptive immune system in animals. In this review, we provide an overview of the resistance mechanisms, evolution, and agricultural applications of R genes against plant viruses. We also introduce recent advances in research into the regulatory mechanisms of R gene expression, focusing on regulation by microRNAs and introns. One of the most intriguing phenomena that occur following R gene-mediated recognition of viruses is programmed cell death around the initial infection site, although its significance in the survival strategies of plants remains to be elucidated. We discuss the possible benefits for plants of inducing such programmed cell death based on our empirical observations and some hypotheses from an ecological point of view.

Although chronic infection of hepatitis C virus (HCV) induces disorders of lipid metabolism, HCV is known to utilize lipid metabolism for efficient propagation in the liver. Due to the morphological and physiological similarities of HCV particles to lipoproteins, lipid-associated HCV particles are named lipoviroparticles. Previous reports have shown that lipoprotein receptors or cholesterol transporter participate in the entry of lipoviroparticles. In addition, recent analyses revealed that exchangeable apolipoproteins directly interact with the viral membrane to generate infectious HCV particles. In this review, we would like to discuss about involvement of lipoprotein and apolipoprotein in HCV lifecycle.