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Volume 54, Issue 1
June
Displaying 1-14 of 14 articles from this issue
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Reviews
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Tsukasa Seya, Masashi Shingai, Misako MatsumotoArticle type: Others
Subject area: Others
2004 Volume 54 Issue 1 Pages 1-8
Published: 2004
Released on J-STAGE: June 17, 2005
JOURNAL FREE ACCESSAnti-viral host defense harbors a variety of strategies to coup with viral infection. Recent findings suggested that Toll-like receptors (TLRs) and their signaling pathways involve type I IFN induction in response to virus-specific molecular patterns. TLR 3 and TLR 4 in myeloid dendritic cells (mDCs) recognize viral dsRNA and putative viral products, respectively, to induce IFN-β via IRF-3 activation. On the other hand, TLR 7 and TLR 9 in plasmacytoid DCs (pDCs) induce IFN-α in response to their ligands, U/G-rich ssRNA and non-methylated CpG DNA. We identified TICAM-1 which is recruited to the cytoplasmic domain (designated TIR) of TLR 3 and allows to select the pathway to activation of IRF-3. We also identified TICAM-2 which binds TLR 4 and together with TICAM-1 activates IRF-3. TICAM-1 knockdown by RNAi supported the key role of TICAM-1 in IFN-β induction. Hence, the IFN-β induction in mDCs appears in part due to the function of TICAM-1. Viruses are known to activate kinases that directly activate IRF-3 inside the cells, and this pathway may merge with the TLR 3-TICAM-1 pathway. Here we review the relationship between the TLR 3-TICAM-1 pathway and viral infection.View full abstractDownload PDF (348K) -
—Viral Glycoproteins on a Raft—Makoto TakedaArticle type: Others
Subject area: Others
2004 Volume 54 Issue 1 Pages 9-15
Published: 2004
Released on J-STAGE: June 17, 2005
JOURNAL FREE ACCESSLipid molecules of the plasma membrane are not distributed homogeneously, but form a lateral organization resulting from preferential packaging of sphingolipid and cholesterol into lipid microdomain rafts, in which specific membrane proteins become incorporated. Evidence has accumulated that a variety of viruses including influenza virus use the raft during some steps of their replication cycles. Influenza virus glycoproteins, hemagglutinin (HA) and neuraminidase, associate intrinsically with the rafts. The HA protein is distributed in clusters at the plasma membrane and concentrated in the small area by interacting with the raft. A mutant influenza virus, whose HA protein lacks the ability to associate with the raft, contains reduced amounts of the HA proteins and exhibits a decreased virus to cell fusion activity, resulting in greatly reduced infectivity. Thus, the raft may play an important role in virus production by acting as a concentrating devise or an efficient carrier to transport the HA protein to the site of virus budding.View full abstractDownload PDF (334K) -
Akio YamadaArticle type: Others
Subject area: Others
2004 Volume 54 Issue 1 Pages 17-22
Published: 2004
Released on J-STAGE: June 17, 2005
JOURNAL FREE ACCESSThe numbers of microbial species that can infect human beings are shown to be 1415, of which 868 species (61%) are zoonotic. Since most of the emerging pathogens (75%) are originated from other animals, public health sectors should be vigilant against the emergence of new zoonotic diseases. Only 33% of zoonoses can spread from human to human after introduction into human population. Various factors such as human demography, ecological change, global transportation and climate change are responsible for the emergence of zoonoses. Even a slight change in the ecological niche where pathogenic organisms thrive would result in the increase of the incidence of the disease.View full abstractDownload PDF (374K)
Special Issue 1 : ‘Virology in Postgenomic Era’
Synposium on 51th Annual Meeting of The Japanese Society for Virology
Synposium on 51th Annual Meeting of The Japanese Society for Virology
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Shinya WatanabeArticle type: Others
Subject area: Others
2004 Volume 54 Issue 1 Pages 23-31
Published: 2004
Released on J-STAGE: June 17, 2005
JOURNAL FREE ACCESSHuman genome project revealed that human genes are derived from 30, 000∼40, 000 species of genetic loci, which had been estimated as approximately 100, 000. The project also promoted devising novel tools that enable us to analyze biological phenomena comprehensively. Microarray technology is a representative of the novel tools in genomics and engages us to explore genome-wide expression levels of genes simultaneously (transcriptome analysis). Here we show transcriptomes obtained from 10 species of cells infected with human cytomegalovirus, as a model virus, by a synthetic DNA microarray system that we have established recently. Our system provides simultaneous and parallel description on alteration of expression of viral and host genes that are represented within a single area on a slide glass. Moreover, we propose a project entitled ‘comparative virology on cellular responses of infected hosts’ that consists of multiple acquisition and integration of trasncriptomes from a combination of several cells and viruses as a panel on the identical platform. The attempt should extract a novel concept in virology from investigation on differences and similarities among influence of a virus on a variety of different cells and conversely among responses of a species of cells against a variety of different viruses.View full abstractDownload PDF (571K) -
Yumi Yamaguchi-KabataArticle type: Others
Subject area: Others
2004 Volume 54 Issue 1 Pages 33-38
Published: 2004
Released on J-STAGE: June 17, 2005
JOURNAL FREE ACCESSThe envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) interacts with receptors on the target cell and mediates virus entry by fusing the viral and cell membranes. To maintain the viral infectivity, amino acids that interact with receptors are expected to be more conserved than the other sites on the protein surface. In contrast to the functional constraint of amino acids for the receptor binding, some amino acid changes in this protein may produce antigenic variations that enable the virus to escape from recognition of the host immune system. Therefore, both positive selection (higher fitness) and negative selection (lower fitness) against amino acid changes are taking place during evolution of surface proteins of parasites To elucidate the evolutionary mechanisms of the whole HIV-1 gp120 envelope glycoprotein at the single site level, we collected and analyzed all available sequence data for the protein. By analyzing 186 sequences of the HIV-1 gp120 (subtype B), we reevaluated amino acid variability at the single site level, and estimated the numbers of synonymous and nonsynonymous substitutions at each codon position to detect positive and negative selection. We identified 33 amino acid positions which may be under positive selection. Some of these positions may form discontinuous epitopes. We also analyzed amino acid sequences to find amino acid positions responsible for usage of the second receptor. We found that, in addition to the V3 loop, amino acid variation at residue 440 in C4 region is clearly linked with the usage of CXCR 4.View full abstractDownload PDF (282K) -
Kengo KitadokoroArticle type: Others
Subject area: Others
2004 Volume 54 Issue 1 Pages 39-47
Published: 2004
Released on J-STAGE: June 17, 2005
JOURNAL FREE ACCESSHuman CD81, which is belonged to tetraspanin family, has been previously identified as a receptor for the hepatitis C virus envelope E 2 glycoprotein. The crystal structure of the human CD81 long extracellular domain, binding site for E 2 glycoprotein, is presented here at 1.6 Å resolution. The tertiary structure of CD81-LEL, which is composed of five alpha-helices, is resemble for a mushroom-shaped molecules (stalk and head subdomains) and forms a dimer in the crystallographic asymmetric unit. The two disulfide bridges, which are conserved all the tetraspanin and are necessary for CD 81-HCV interaction, are stabilizing the conformation of the head domain. This head domain is solvent exposed surface region and is locating the amino acid residues which are essential for the E 2 binding. The hydrophobic cluster in this head domain may suggest that the presence of a docking site for a low complementary surface cavity in the partner E 2 glycoprotein. We proposed that the dimer structure may be important in the interactions of HCV E 2 glycoprotein and also the viral protein may occur in dimeric aggregation on the HCV envelope. This common structural motif of the tetraspanin provides the first insight onto the mechanism of HCV binding to human cell and may be targets for structure-based antiviral drug.View full abstractDownload PDF (527K)
Special Issue 2 : ‘Basic Virology to Clinical Medicine’
Synposium on 51th Annual Meeting of The Japanese Society for Virology
Synposium on 51th Annual Meeting of The Japanese Society for Virology
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Keiya OzawaArticle type: Others
Subject area: Others
2004 Volume 54 Issue 1 Pages 49-57
Published: 2004
Released on J-STAGE: June 17, 2005
JOURNAL FREE ACCESSThe success of hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency (X-SCID) was a major breakthrough in the field of gene therapy. However, two patients treated with this gene therapy developed leukemia at a later time, and retroviral vector-mediated gene transfer was considered to trigger leukemogenesis ; i.e. insertional mutagenesis caused activation of LMO 2 gene, which was one step toward leukemia development. To cope with this serious problem, basic studies are required to improve the safety of retroviral vectors and to develop the method for site-specific integration of transgenes. In addition, we have to develop technologies such as selective amplifier genes (SAGs), the system for selective expansion of transduced cells, in order to obtain therapeutic efficacy of hematopoietic stem cell gene therapy in many other disorders. Moreover, clinical applications of AAV vector are promising from the standpoint of safety issue, because this vector is derived from non-pathogenic virus. AAV vector is appropriate for gene transfer into neurons, muscles, and hepatocytes. For example, gene therapy for Parkinson's disease is investigated using AAV vectors. Genetic manipulation is also one of the indispensable technologies in the field of regeneration medicine, and further promotion of basic research is important.View full abstractDownload PDF (408K) -
Masanori BabaArticle type: Others
Subject area: Others
2004 Volume 54 Issue 1 Pages 59-66
Published: 2004
Released on J-STAGE: June 17, 2005
JOURNAL FREE ACCESSEstablishment of highly active antiretroviral therapy (HAART) has brought about dramatic improvement of the prognosis of HIV-1 infection. On the other hand, several drawbacks associated with long-term HARRT have been demonstrated. Among them, emergence of drug-resistant viruses is a serious problem ; therefore compounds with novel mechanisms of action have been investigated to overcome the problem. Novel reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs) recently approved for clinical use are effective against existing resistant strains by once daily administration. In addition, the virus entry (fusion) inhibitor has also been licensed. Since this compound targets a molecule other than reverse transcriptase and protease for inhibition of HIV-1 replication, it is active against HIV-1 highly resistant to RTIs and PIs. Furthermore, clinical trials with CCR 5 (coreceptor of HIV-1) antagonists are in progress, and inhibitors of integrase, HIV-1 gene expression, and virion assembly have been identified.View full abstractDownload PDF (333K) -
Mari KannagiArticle type: Others
Subject area: Others
2004 Volume 54 Issue 1 Pages 67-74
Published: 2004
Released on J-STAGE: June 17, 2005
JOURNAL FREE ACCESSAdult T-cell leukemia (ATL) occurs in a small population of human T-cell leukemia virus type I (HTLV-I)-infected individuals. It has been noted that ATL is incidentally associated with mother-to-child infection which occurs mainly through breast-feeding, elevated levels of proviral load, and insufficiency in HTLV-I-specific cytotoxic T lymphocyte (CTL) responses. Among these, anti-tumor potentials of HTLV-I-specific CTL have been shown in ex vivo analysis of human HTLV-I-infected individuals and also in vivo experiments by using rat models of HTLV-I-infected lymphomas. In another rat model of HTLV-I-infection, orally infected rats showed significantly higher HTLV-I proviral load but lower HTLV-I-specific cellular immune responses than in intraperitoneally infected rats. As a result, persistent viral load was inversely correlated with levels of virus-specific T-cell responses. HTLV-I-specific T-cell responses in orally infected rats recovered by re-immunization. Conversion of Tax-specific T-cell responses from low to high levels was also observed in an ATL patient who obtained complete remission after hematopoietic stem cell transplantation. These findings suggest that HTLV-I-specific immune unresponsiveness associated with oral HTLV-I infection may be a potential risk factor for development of ATL, allowing expansion of the infected cell reservoir in vivo, and that immunological strategies targeting Tax may potentially reduce the risk of ATL and induce therapeutic effects on ATL.View full abstractDownload PDF (351K) -
Masanori Hayami, Reii HoriuchiArticle type: Others
Subject area: Others
2004 Volume 54 Issue 1 Pages 75-82
Published: 2004
Released on J-STAGE: June 17, 2005
JOURNAL FREE ACCESSA great effort for developing AIDS vaccine has been carried out in the world, designed by various new ideas based on basic research information obtained in recent virology and immunology. Withall it, to obtain effective AIDS vaccine is considered skeptical. One of the reasons of its difficulty is a lack of experimental animals susceptible to HIV-1. In our laboratory, we have succeeded in developing chimeric SIV having 3′ half of HIV-1 genome including env (SHIV), which is infectious to macaque monkeys. One of SHIVs has been proved nonpathogenic in monkeys from various aspects and it afforded protective immunity to monkeys against pathogenic SHIV challenge infection.
Now, we are trying to develop anti-HIV live attenuated vaccines using the nonpathogenic SHIV as a starting material. In the history of virus vaccine, live attenuated vaccines have been proved most effective in measles and polio-myelitis. However, it is not clear whether nonpathogenic HIV exists or not. Futhermore, even if nonpathogenic HIV could be obtained, there is possibility that it will easily mutate to pathogenic one. Therefore, to develop live attenuated AIDS vaccine is considered dangerous.
In this article, We will introduce our research on SHIV pathogenicity using monkeys and hypothesize possibility to obtain nonpathogenic HIV which is speculated from the origin and evolution of HIV/SIV. To clarify virulence and nonvirulence of HIV and to obtain nonpathogenic virus are not only applied research but also basic science to dissolve the fundemental question why HIV can induce the disease.View full abstractDownload PDF (355K)
SUGIURA Memorial Incentive Award for Young Virologist, The Japanese Society for Virology, 2003
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Hideo GotoArticle type: Others
Subject area: Others
2004 Volume 54 Issue 1 Pages 83-91
Published: 2004
Released on J-STAGE: June 17, 2005
JOURNAL FREE ACCESSBecause cleavage of the hemagglutinin (HA) molecule by proteases is a prerequisite for infectivity of influenza A viruses, this molecule is a major determinant of viral pathogenicity. Although well documented in the pathogenicity of avian influenza viruses, the role of HA cleavage in the pathogenicity of mammalian viruses is not well understood. Therefore, we studied a mouse-adapted human isolate A/WSN/33 (WSN), a neurovirulent influenza virus strain that causes systemic infection when inoculated intranasally into mice. We found a novel mechanism of HA cleavage for WSN virus : the neuraminidase (NA) of WSN virus binds and sequesters plasminogen on the cell surface, leading to enhanced cleavage of the HA. The structural basis of this novel function of the NA molecule appears to be the presence of a carboxyl-terminal lysine and the absence of an oligosaccharide side chain at position 146. To obtain direct evidence that the plasminogen-binding activity of the NA enhances the pathogenicity of WSN virus, we generated mutant viruses that are deficient in plasminogen-binding activity by reverse genetics. The mutant viruses showed attenuated growth in mice and failed to grow at all in the brains of these animals. Therefore, we concluded that the novel function of plasminogen-binding activity of the NA determines the pathogenicity of WSN virus in mice.View full abstractDownload PDF (514K)
Topics
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Hiroshi KidaArticle type: Others
Subject area: Others
2004 Volume 54 Issue 1 Pages 93-96
Published: 2004
Released on J-STAGE: June 17, 2005
JOURNAL FREE ACCESSRecent outbreaks of highly pathogenic avian influenza in chickens and ducks that occurred in 9 Asian countries including Japan alarmed to realize that there is no border for infections and gave a rise to great concern for human health as well as for agriculture. This H5N1 virus jumped the species barrier and caused severe disease with high mortality in humans in Viet Nam and Thailand ; 15 deaths of 22 cases and 8 of 12, respectively.
A second concern was the possibility that the situation could give rise to another influenza pandemic in humans since genetic reassortment may occur between avian and human influenza viruses when a person is concurrently infected with viruses from both species. This process of gene swapping inside the human body can give rise to a new subtype of the influenza virus to which humans would not have immunity. The outbreaks also emphasized the need to continue active surveillance on avian influenza throughout the year to undertake aggressive emergency control measures as soon as an infection is detected.View full abstractDownload PDF (268K) -
Tetsuya MizutaniArticle type: Others
Subject area: Others
2004 Volume 54 Issue 1 Pages 97-105
Published: 2004
Released on J-STAGE: June 17, 2005
JOURNAL FREE ACCESSThe serious respiratory disease, SARS (Severe Acute Respiratory Syndrome), outbreaking in winter of 2003 to 2004 remained in a sporadic patient's generating at this winter. However, there is also a possibility that wild animals as the source of infection may not be specified and that it may be much in fashion again. The paper regarding SARS and SARS-CoV is published at one per day now which has passed since fashion of SARS in one or so year. There are many papers which the researchers of other viruses enter into the research field of SARS-CoV using their own technology in addition to the researchers of coronavirus. Topics of the research on the present SARS-research field are development of vaccine, inspecting of medicine and establishment of diagnostic method. Here, the newest information is offered about these researches.View full abstractDownload PDF (422K) -
—A simple and rapid gene amplification method—Hiroshi UshikuboArticle type: Others
Subject area: Others
2004 Volume 54 Issue 1 Pages 107-112
Published: 2004
Released on J-STAGE: June 17, 2005
JOURNAL FREE ACCESSSo far nucleic acid test (NAT) has been employed in various fields, including infectious disease diagnoses. However, due to its complicated procedures and relatively high cost, it has not been widely utilized in many actual diagnostic applications. We have therefore developed a simple and rapid gene amplification technology, Loop-mediated Isothermal Amplification (LAMP) method, which has shown prominent results of surpassing the performance of the conventional gene amplification methods. LAMP method acquires three main features : (1) all reaction can be carried out under isothermal conditions ; (2) the amplification efficiency is extremely high and tremendous amount of amplification products can be obtained ; and (3) the reaction is highly specific. Furthermore, developed from the standard LAMP method, a rapid LAMP method, by adding in the loop primers, can reduce the amplification time from the previous 1 hour to less than 30 minutes. Enormous amount of white precipitate of magnesium pyrophosphate is produced as a by-product of the amplification, therefore, direct visual detection is possible without using any reaction indicators and detection equipments. We believe LAMP technology, with the integration of these features, can rightly apply to clinical genetic testing, food and environmental analysis, as well as NAT in different fields.View full abstractDownload PDF (327K)
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