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Volume 58, Issue 1
Displaying 1-10 of 10 articles from this issue
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Reviews
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Takao HASHIGUCHI, Katsumi MAENAKA, Yusuke YANAGI2008 Volume 58 Issue 1 Pages 1-10
Published: June 30, 2008
Released on J-STAGE: December 28, 2008
JOURNAL FREE ACCESSX-ray crystallographic analyses, together with nuclear magnetic resonance, have revealed three-dimensional structures of many important viral proteins, thereby allowing us to better understand the interactions between viral and host cell molecules. In this review, we summarize the recently determined crystal structure of the measles virus (MV) attachment protein hemagglutinin. Based on this structural information, we also discuss how the MV hemagglutinin interacts with various cellular receptors and why MV vaccines have been effective for many years without inducing escape mutant viruses. Other topics discussed are a putative MV receptor present on polarized epithelial cells and the protein expression system using a cultured human cell line 293SGnTI(-), which is suitable for X-ray crystallographic analyses.View full abstractDownload PDF (2229K) -
Toshiyoshi FUJIWARA, Noriaki TANAKA2008 Volume 58 Issue 1 Pages 11-18
Published: June 30, 2008
Released on J-STAGE: December 28, 2008
JOURNAL FREE ACCESSReplication-selective tumor-specific viruses present a novel approach for treatment of neoplastic disease. Telomerase activation is considered to be a critical step in carcinogenesis and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. We constructed an attenuated adenovirus 5 vector (Telomelysin, OBP-301), in which the hTERT promoter element drives expression of E1 genes. Telomelysin replicated efficiently and induced marked cell killing in a panel of human cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal human cells lacking telomerase activity. We further modified the E3 region of OBP-301 to contain green fluorescent protein (GFP) gene for monitoring viral replication (TelomeScan, OBP-401). When TelomeScan was intratumorally injected into human tumors orthotopically implanted into the rectum in mice, para-aortic lymph node metastasis could be visualized at laparotomy under a three-chip color cooled charged-coupled device camera. This article reviews recent highlights in this rapidly evolving field: cancer therapeutic and cancer diagnostic approaches using the telomerase-specific oncolytic adenoviruses.View full abstractDownload PDF (397K)
Special Issue 1 : Innate Immunity and Viral Infection
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Takashi EBIHARA, Misako MATSUMOTO, Tsukasa SEYA2008 Volume 58 Issue 1 Pages 19-26
Published: June 30, 2008
Released on J-STAGE: December 28, 2008
JOURNAL FREE ACCESSHepatitis C virus (HCV) is a single-strand, positive sense RNA virus belonging to the flaviviridae family. HCV develops persistent infection in >70% of infected patients, and eventually causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma in some patients. Once chronic infection is established in patients with HCV, spontaneous viral clearance fails, although how HCV remains persistently infecting the liver is largely unknown. Insufficient immune response, involving antiviral innate immune response including dendritic cells (DCs), has been focused. A number of controversial studies have been reported as to HCV genome replication and HCV-mediated immune responses in human DCs. A tantalizing point of these earlier studies is the lack of the system for viral propagation in HCV. Recently, an in vitro system was exploited to propagate HCV particles using the JFH1 strain. In this review, we review the previous reports about the subversion of innate immunity by HCV and show the innate response of monocyte-derived dendritic cells (MoDCs) against the JFH1 strain. We could not observe HCV direct interaction with MoDC maturation. MoDCs maturated by phagocytosing HCV-infected apoptotic cells containing virus-derived dsRNA, which interacted with TLR3 in the phagosomes. All of these data suggests the importance of TLR3 signal for the induction of anti-HCV innate immunity.View full abstractDownload PDF (252K) -
Takeshi SATOH, Hisashi ARASE2008 Volume 58 Issue 1 Pages 27-36
Published: June 30, 2008
Released on J-STAGE: December 28, 2008
JOURNAL FREE ACCESSPaired receptors that consist of highly related activating and inhibitory receptors are widely involved in the regulation of immune response. Several viruses that persistently infect hosts possess genes that encode ligands for inhibitory receptors in order to escape from host immune system. Herpes simplex virus type 1 (HSV-1) is one of the viruses that cause persistent infection. Here, we found that HSV-1-infected cells express a ligand for paired immunoglobulin like-type 2 receptor (PILR)α, one of paired inhibitory receptors mainly expressed on myeloid cells such as monocytes, macrophages and dendritic cells. Furthermore, we have identified that glycoprotein B (gB), an envelope protein of HSV-1, is a ligand for PILRα by mass spectrometry analysis. Because gB is essential for HSV-1 to infect cells, we analyzed function of PILRα in HSV-1 infection. When PILRα was transfected into CHO-K1 cells, which is resistant to HSV-1 infection, the PILRα-transfected CHO-K1 cells became permissive to HSV-1 infection. We further addressed weather PILRα is involved in the HSV-1 infection of primary human cells. CD14-positive monocytes that express both PILRα and HVEM, a glycoprotein D receptor, were susceptible to HSV-1 infection. In contrast, HSV-1 did not infect CD14-negative lymphocytes that express HVEM but not PILRα. Furthermore, HSV-1 infection of monocyte was blocked by both anti-PILRα mAb and anti-HVEM antiserum. These findings indicated that both gB and gD receptors play an important role in HSV-1 infection. We have shown, for the first time, that viruses use an inhibitory immune receptor to enter a cell. Invasion into hematopoietic cells by using inhibitory receptors should be beneficial to the virus because binding to inhibitory receptors may not only provide entry, but also trigger the inhibitory receptor to suppress the immune functions of the infected cell.View full abstractDownload PDF (536K) -
Akinori TAKAOKA, Shigeki SHINOHARA2008 Volume 58 Issue 1 Pages 37-46
Published: June 30, 2008
Released on J-STAGE: December 28, 2008
JOURNAL FREE ACCESSMicrobial sensing mediated by pattern recognition receptors (PRRs) is the first key step to trigger innate immune responses, represented by the induction of type I interferons (IFNs), proinflammatory cytokines and chemokines. This innate signaling elicits an efficient activation of more specific responses in adaptive immunity. Such coordinated responses in the two systems are essential for the optimal elimination of invading microbes. Despite a major advance in our understanding of RNA sensors, TLR9 remained the only known sensor of DNA. On the other hand, there has been accumulating evidence supporting the existence of TLR9-independent DNA recognition mechanism. In this regard, DAI (also termed as DLM-1/ZBP1), the first sensor of cytosolic DNA, has recently been identified with its activation of IFN-regulatory factors(IRFs) and NF-κB transcriptional factors. Several recent papers suggest the involvement of an additional cytosolic DNA sensor(s). There is also a recent report that cytosolic microbial and host DNA can trigger pro-inflammatory responses via the TLR- and IRF-indepnedent pathway mediated by the inflammasome, which is consisted of NLR family members together with the adaptor protein ASC and caspase-1. In addition, evidence has been provided that host- and virus-derived proteins, which contain DNA-binding motifs (Zα and/or Zβ) similar to those of DAI(DLM-1/ZBP1), negatively regulates the immune response that is activated by cytosolic DNA. Thus, these recent findings reveal the complex DNA-sensing mechanism for triggering the activation of innate immunity, and the breakdown of this sensing mechanism may lead to autoimmune abnormalities.View full abstractDownload PDF (1920K) -
Kei-ichiro ARIMOTO, Kunitada SHIMOTOHNO2008 Volume 58 Issue 1 Pages 47-54
Published: June 30, 2008
Released on J-STAGE: December 28, 2008
JOURNAL FREE ACCESSAs a defense mechanism against infection, host cells have evolved sensor molecules which detect pathogen components directly and induce protective responses against the infection. TLRs, well known receptors, recognize a pathogen on the surface of cells or endosome/lysosome. Many pathogens penetrate into cytoplasm, in where non-TLR sensors recognize pathogen components including double-stranded RNA (dsRNA). On the downstream of each sensor, a variety of functional signaling molecules are activated to produce various cytokines upon the microbial invasion to induce host defense responses. Because that cytokines produced to regulate the host defense responses are known to affect cell proliferation also, the level of these molecules are needed to be controlled tightly, which means requisites of negative regulation of the signaling activated by pathogen after the completion of proper immune responses. Recent studies suggest important roles of some ubiquitin systems in this regulation. Here we focus, in particular, ubiquitin conjugation to signaling molecules by virus activation and like to show how ubiquitin signaling plays roles in this regulation by introducing some recent works.View full abstractDownload PDF (468K)
Special Issue 2 : RNA Silencing
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Haruhiko SIOMI2008 Volume 58 Issue 1 Pages 55-60
Published: June 30, 2008
Released on J-STAGE: December 28, 2008
JOURNAL FREE ACCESSIt is remarkable to consider that more than 40% of the human genome is comprised of transposable elements (TEs) and their relics. TEs were long thought of as either 'selfish' or 'parasitic' DNA elements that were there not for the sake of the host organism, but for their own sake in an evolutionary sense; thus they were considered to be either neutral or deleterious to their hosts. However, it is becoming increasingly clear that there are more complex interactions between TEs and their hosts than strict parasitism; these elements produce changes that have a broad range of fitness values at an organismal level. Recent evidence indicates that these elements confer a fitness benefit to the host more frequently than previously recognized. RNA silencing is thought to have evolved as a form of nucleic-acid-based, and thus sequence-directed, immunity to block the action of viruses and TEs. Host-parasite interactions are typically associated with rapid evolution because of a permanent antagonistic relationship resembling an "arms race" in which parasite adaptations are countered by host adaptations. Complex interactions between TEs and RNA silencing machineries have been co-opted to regulate cellular genes.View full abstractDownload PDF (210K) -
Akira MINE, Tetsuro OKUNO2008 Volume 58 Issue 1 Pages 61-68
Published: June 30, 2008
Released on J-STAGE: December 28, 2008
JOURNAL FREE ACCESSSmall RNAs play a critical role in the regulation of gene expression in diverse cellular processes. This mechanism, termed RNA silencing or RNAi, also functions as a defense mechanism against molecular parasites such as virus and transposon. Whereas RNA silencing is triggered by viral infection, viruses suppress RNA silencing to establish infection, and sometimes even exploit it for their infection. In this mini review, we describe intimate interactions between viruses and host organisms in RNA silencing.View full abstractDownload PDF (345K)
SUGIURA Memorial Incentive Award for Young Virologist,The Japanese Society for Virology,2007
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Kyoko SHINYA2008 Volume 58 Issue 1 Pages 69-72
Published: June 30, 2008
Released on J-STAGE: December 28, 2008
JOURNAL FREE ACCESSInfluenza A viruses are a member of Orthomyxoviridae possessing negative-sense, single-stranded, and 8 segmented RNA genomes. These 8 RNA segments encode individual specific viral proteins, and up until now a total of 11 proteins have been identified including alternate open reading frame in one genome. Because of this simplicity, utilization of many host systems is required during the viral infection cycle in a cell. Therefore adaptation to the host cell system is the most important issue for the influenza A virus infection and transmission. Although there are many factors which relate to the host adaptation in the viruses themselves, elucidation of mechanisms about changing viral receptor specificities is one of the most advanced research areas. Because the avian type viral receptor was found in the human lungs, the situation, such as co-existence of avian- and human-derived viral receptors in the human airway, may contribute to the human adaptation of avian derived influenza A viruses.View full abstractDownload PDF (192K) -
Koichi WATASHI2008 Volume 58 Issue 1 Pages 73-80
Published: June 30, 2008
Released on J-STAGE: December 28, 2008
JOURNAL FREE ACCESSIt is one of the major subjects in the virology field to develop novel anti-viral strategies as well as to reveal the mechanism of viral replication. We have developed a method of chemical compound-directed analysis on viral replication. Until now, we rediscovered cyclosporin A and tamoxifen as anti-hepatitis C virus (HCV) compounds. Through analysis using these compounds, it was revealed that host cell factors cyclophilin (CyP) and estrogen receptor were important for HCV replication. CyP was demonstrated to serve as a new target of the development for anti-HCV agents and CyP inhibitors are now under clinical trials. Thus, an application of chemical biology to virology would provide not only mechanistic aspects of viral life cycles but also new anti-viral strategies.View full abstractDownload PDF (311K)
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